Selectivity of bovine interleukin-2 mutein stimulation on bovine peripheral blood mononuclear cells
Delivery of engineered interleukin-2 (IL-2) variants (muteins) is thought to be a promising cancer therapy in humans and mice. Our previous study indicated that bovine IL-2 (boIL-2) has a great potential to elicit NK cell activity for which distribution of IL-2 receptors on the target cell surface i...
Saved in:
Published in | Journal of Veterinary Medical Science Vol. 87; no. 7; pp. 781 - 790 |
---|---|
Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Japan
JAPANESE SOCIETY OF VETERINARY SCIENCE
2025
Japan Science and Technology Agency The Japanese Society of Veterinary Science |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Abstract | Delivery of engineered interleukin-2 (IL-2) variants (muteins) is thought to be a promising cancer therapy in humans and mice. Our previous study indicated that bovine IL-2 (boIL-2) has a great potential to elicit NK cell activity for which distribution of IL-2 receptors on the target cell surface influences signal transduction. We developed nine boIL-2 muteins and examined the influence of the muteins on bovine peripheral blood mononuclear cells in vitro. On bovine peripheral mononuclear cells, NK cells strongly expressed CD122, followed by CD8+ T cells, while CD4+ T cells and γδ T cells did not show significant CD122 expression. All boIL-2 muteins showed decreasing in binding to boIL-2 receptor α, CD25, while maintaining their ability to bind to boIL-2 receptor βγ, CD122/CD132, heterodimer. The mutein F44A and E63A suppressed CD4+ T cell expansion but maintained the NK cell expansion. These results indicate that boIL-2 muteins can alter immunological outcomes and may be used for clinical intervention for a disease progression. |
---|---|
AbstractList | Delivery of engineered interleukin-2 (IL-2) variants (muteins) is thought to be a promising cancer therapy in humans and mice. Our previous study indicated that bovine IL-2 (boIL-2) has a great potential to elicit NK cell activity for which distribution of IL-2 receptors on the target cell surface influences signal transduction. We developed nine boIL-2 muteins and examined the influence of the muteins on bovine peripheral blood mononuclear cells in vitro. On bovine peripheral mononuclear cells, NK cells strongly expressed CD122, followed by CD8+ T cells, while CD4+ T cells and γδ T cells did not show significant CD122 expression. All boIL-2 muteins showed decreasing in binding to boIL-2 receptor α, CD25, while maintaining their ability to bind to boIL-2 receptor βγ, CD122/CD132, heterodimer. The mutein F44A and E63A suppressed CD4+ T cell expansion but maintained the NK cell expansion. These results indicate that boIL-2 muteins can alter immunological outcomes and may be used for clinical intervention for a disease progression. Delivery of engineered interleukin-2 (IL-2) variants (muteins) is thought to be a promising cancer therapy in humans and mice. Our previous study indicated that bovine IL-2 (boIL-2) has a great potential to elicit NK cell activity for which distribution of IL-2 receptors on the target cell surface influences signal transduction. We developed nine boIL-2 muteins and examined the influence of the muteins on bovine peripheral blood mononuclear cells in vitro . On bovine peripheral mononuclear cells, NK cells strongly expressed CD122, followed by CD8 + T cells, while CD4 + T cells and γδ T cells did not show significant CD122 expression. All boIL-2 muteins showed decreasing in binding to boIL-2 receptor α, CD25, while maintaining their ability to bind to boIL-2 receptor βγ, CD122/CD132, heterodimer. The mutein F44A and E63A suppressed CD4 + T cell expansion but maintained the NK cell expansion. These results indicate that boIL-2 muteins can alter immunological outcomes and may be used for clinical intervention for a disease progression. Delivery of engineered interleukin-2 (IL-2) variants (muteins) is thought to be a promising cancer therapy in humans and mice. Our previous study indicated that bovine IL-2 (boIL-2) has a great potential to elicit NK cell activity for which distribution of IL-2 receptors on the target cell surface influences signal transduction. We developed nine boIL-2 muteins and examined the influence of the muteins on bovine peripheral blood mononuclear cells in vitro. On bovine peripheral mononuclear cells, NK cells strongly expressed CD122, followed by CD8+ T cells, while CD4+ T cells and γδ T cells did not show significant CD122 expression. All boIL-2 muteins showed decreasing in binding to boIL-2 receptor α, CD25, while maintaining their ability to bind to boIL-2 receptor βγ, CD122/CD132, heterodimer. The mutein F44A and E63A suppressed CD4+ T cell expansion but maintained the NK cell expansion. These results indicate that boIL-2 muteins can alter immunological outcomes and may be used for clinical intervention for a disease progression.Delivery of engineered interleukin-2 (IL-2) variants (muteins) is thought to be a promising cancer therapy in humans and mice. Our previous study indicated that bovine IL-2 (boIL-2) has a great potential to elicit NK cell activity for which distribution of IL-2 receptors on the target cell surface influences signal transduction. We developed nine boIL-2 muteins and examined the influence of the muteins on bovine peripheral blood mononuclear cells in vitro. On bovine peripheral mononuclear cells, NK cells strongly expressed CD122, followed by CD8+ T cells, while CD4+ T cells and γδ T cells did not show significant CD122 expression. All boIL-2 muteins showed decreasing in binding to boIL-2 receptor α, CD25, while maintaining their ability to bind to boIL-2 receptor βγ, CD122/CD132, heterodimer. The mutein F44A and E63A suppressed CD4+ T cell expansion but maintained the NK cell expansion. These results indicate that boIL-2 muteins can alter immunological outcomes and may be used for clinical intervention for a disease progression. Delivery of engineered interleukin-2 (IL-2) variants (muteins) is thought to be a promising cancer therapy in humans and mice. Our previous study indicated that bovine IL-2 (boIL-2) has a great potential to elicit NK cell activity for which distribution of IL-2 receptors on the target cell surface influences signal transduction. We developed nine boIL-2 muteins and examined the influence of the muteins on bovine peripheral blood mononuclear cells in vitro. On bovine peripheral mononuclear cells, NK cells strongly expressed CD122, followed by CD8 T cells, while CD4 T cells and γδ T cells did not show significant CD122 expression. All boIL-2 muteins showed decreasing in binding to boIL-2 receptor α, CD25, while maintaining their ability to bind to boIL-2 receptor βγ, CD122/CD132, heterodimer. The mutein F44A and E63A suppressed CD4 T cell expansion but maintained the NK cell expansion. These results indicate that boIL-2 muteins can alter immunological outcomes and may be used for clinical intervention for a disease progression. |
ArticleNumber | 24-0470 |
Author | NORIMINE, Junzo UTO, Tomofumi SEKIGUCHI, Satoshi SATO, Katsuaki TOMINAGA, Moe FUKAYA, Tomohiro MITOMA, Shuya |
Author_xml | – sequence: 1 fullname: MITOMA, Shuya organization: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan – sequence: 2 fullname: UTO, Tomofumi organization: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan – sequence: 3 fullname: FUKAYA, Tomohiro organization: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan – sequence: 4 fullname: TOMINAGA, Moe organization: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan – sequence: 5 fullname: SEKIGUCHI, Satoshi organization: Department of Veterinary Sciences, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan – sequence: 6 fullname: SATO, Katsuaki organization: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan – sequence: 7 fullname: NORIMINE, Junzo organization: Center for Animal Disease Control, University of Miyazaki, Miyazaki, Japan |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/40451851$$D View this record in MEDLINE/PubMed |
BookMark | eNpdkc2LFDEQxYOsuLOrN88S8OLBXvPZ6ZxEF79gwYN6Dul09U7G7mRM0gP735tmxkGFkFDUL49X9a7QRYgBEHpOyQ1lmr3ZHeZ8w0RDhCKP0IZyoRoluL5AG6Jp2ygmySW6ynlHCKOi1U_QpSBC0k7SDXLfYAJX_MGXBxxH3MeDD4B9KJAmWH760DA8LwV8wLn4eZls8THgek7oHpLfbyHZCfdTjAOeY3W4uAlswg6mKT9Fj0c7ZXh2eq_Rj48fvt9-bu6-fvpy--6ucVJ3pQGpAJQgHTg7jkIOYtQdG4jThEHHB6cHJXnf927kbd8pzkmvOmGVGGpRiWv09qi7X_oZBgehVFdmn_xs04OJ1pt_O8FvzX08GMqYaGW3Krw6KaT4a4FczOzzOoMNEJdseF1g3SfluqIv_0N3cUmhzlcprluiWyor9eJvS2cvfwKowOsj4FLMOcF4Rigxa75mzdcwYdZ8K_7-iO9ysfdwhm0qvm78CHfKqPU6fTo33dYmA4H_BiRXst4 |
Cites_doi | 10.1093/nar/gky427 10.1006/jmbi.1994.0194 10.1016/S0378-1135(00)00238-8 10.4049/jimmunol.1303398 10.1038/nri2580 10.1292/jvms.12-0100 10.1016/S1074-7613(00)80564-6 10.3389/fimmu.2022.974188 10.1016/j.immuni.2015.04.018 10.1073/pnas.0511161103 10.1136/jitc-2022-006409 10.1073/pnas.88.11.4636 10.1371/journal.pcbi.1008667 10.1016/j.vetmic.2005.09.004 10.3389/fvets.2017.00112 10.1371/journal.pone.0102191 10.1073/pnas.1525098113 10.1016/j.ijrobp.2019.07.054 10.1073/pnas.1002569107 10.1111/cas.15127 10.1111/j.1439-0450.1997.tb01013.x 10.1002/cncr.23552 10.1038/s41598-017-09654-8 10.3389/fimmu.2022.1021828 10.1038/s41467-023-37825-x 10.1038/s41467-022-31130-9 10.4049/jimmunol.1201895 10.4049/jimmunol.181.9.5940 10.1016/j.molimm.2021.02.028 10.1128/JVI.73.10.8427-8434.1999 10.1016/0165-2427(94)90042-6 10.1158/1078-0432.CCR-08-0116 10.1016/j.vetimm.2016.10.013 10.1111/j.1749-6632.1979.tb47136.x 10.1016/j.jcyt.2012.12.004 10.1016/j.it.2015.10.003 10.1016/j.jim.2007.11.012 10.1038/s41598-018-25383-y 10.1146/annurev.immunol.26.021607.090357 10.4049/jimmunol.174.6.3386 10.1002/j.1460-2075.1993.tb06206.x 10.1016/j.immuni.2008.04.022 10.1002/iid3.93 10.1371/journal.pone.0151083 10.1089/lrb.2016.0026 10.1038/s41392-022-01208-3 10.4049/jimmunol.0901334 10.1016/0165-2427(93)90013-T 10.1292/jvms.20-0423 10.1126/science.1117893 10.1111/j.1432-1033.1989.tb14647.x 10.3168/jds.2016-11144 10.1073/pnas.2117401119 10.1016/S0264-410X(98)00041-3 10.1016/0165-2427(89)90110-4 10.1016/0092-8674(93)90152-G |
ContentType | Journal Article |
Copyright | 2025 by the Japanese Society of Veterinary Science 2025. This work is published under https://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2025 The Japanese Society of Veterinary Science 2025 |
Copyright_xml | – notice: 2025 by the Japanese Society of Veterinary Science – notice: 2025. This work is published under https://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: 2025 The Japanese Society of Veterinary Science 2025 |
DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QR 7U9 8FD FR3 H94 M7N P64 7X8 5PM |
DOI | 10.1292/jvms.24-0470 |
DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Chemoreception Abstracts Virology and AIDS Abstracts Technology Research Database Engineering Research Database AIDS and Cancer Research Abstracts Algology Mycology and Protozoology Abstracts (Microbiology C) Biotechnology and BioEngineering Abstracts MEDLINE - Academic PubMed Central (Full Participant titles) |
DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Virology and AIDS Abstracts Technology Research Database Algology Mycology and Protozoology Abstracts (Microbiology C) AIDS and Cancer Research Abstracts Chemoreception Abstracts Engineering Research Database Biotechnology and BioEngineering Abstracts MEDLINE - Academic |
DatabaseTitleList | Virology and AIDS Abstracts MEDLINE - Academic MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | fulltext_linktorsrc |
Discipline | Veterinary Medicine |
EISSN | 1347-7439 |
EndPage | 790 |
ExternalDocumentID | PMC12246588 40451851 10_1292_jvms_24_0470 article_jvms_87_7_87_24_0470_article_char_en |
Genre | Journal Article |
GroupedDBID | 29L 2WC 53G 5GY ACGFO ACIWK ACPRK ADBBV ADRAZ AENEX AFRAH AI. ALMA_UNASSIGNED_HOLDINGS AOIJS B.T BAWUL CS3 DIK DU5 E3Z EBS ECGQY EJD EYRJQ HYE JSF JSH KQ8 M48 N5S OK1 OVT P2P PGMZT RJT RNS RPM RZJ TKC TR2 VH1 XSB AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QR 7U9 8FD FR3 H94 M7N P64 7X8 5PM |
ID | FETCH-LOGICAL-c598t-e57ee7408ecaff45d4f982d0c902e83dc9d753bbbcf36b87330b784a74d873e83 |
IEDL.DBID | M48 |
ISSN | 0916-7250 1347-7439 |
IngestDate | Thu Aug 21 18:23:15 EDT 2025 Sun Jun 29 02:50:51 EDT 2025 Fri Aug 15 06:41:11 EDT 2025 Mon Jul 21 06:04:52 EDT 2025 Wed Jul 16 16:47:32 EDT 2025 Thu Aug 07 14:07:48 EDT 2025 |
IsDoiOpenAccess | true |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 7 |
Keywords | bovine interleukin-2 mutein selective stimulation natural killer cell CD122 |
Language | English |
License | This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/) |
LinkModel | DirectLink |
MergedId | FETCHMERGED-LOGICAL-c598t-e57ee7408ecaff45d4f982d0c902e83dc9d753bbbcf36b87330b784a74d873e83 |
Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
OpenAccessLink | http://journals.scholarsportal.info/openUrl.xqy?doi=10.1292/jvms.24-0470 |
PMID | 40451851 |
PQID | 3239609615 |
PQPubID | 2028964 |
PageCount | 10 |
ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_12246588 proquest_miscellaneous_3214725139 proquest_journals_3239609615 pubmed_primary_40451851 crossref_primary_10_1292_jvms_24_0470 jstage_primary_article_jvms_87_7_87_24_0470_article_char_en |
PublicationCentury | 2000 |
PublicationDate | 2025-00-00 |
PublicationDateYYYYMMDD | 2025-01-01 |
PublicationDate_xml | – year: 2025 text: 2025-00-00 |
PublicationDecade | 2020 |
PublicationPlace | Japan |
PublicationPlace_xml | – name: Japan – name: Tokyo |
PublicationTitle | Journal of Veterinary Medical Science |
PublicationTitleAlternate | J. Vet. Med. Sci. |
PublicationYear | 2025 |
Publisher | JAPANESE SOCIETY OF VETERINARY SCIENCE Japan Science and Technology Agency The Japanese Society of Veterinary Science |
Publisher_xml | – name: JAPANESE SOCIETY OF VETERINARY SCIENCE – name: Japan Science and Technology Agency – name: The Japanese Society of Veterinary Science |
References | 4. Bertoni M, Kiefer F, Biasini M, Bordoli L, Schwede T. 2017. Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology. Sci Rep 7: 10480. 12. Frie MC, Sporer KRB, Benitez OJ, Wallace JC, Droscha CJ, Bartlett PC, Coussens PM. 2017. Dairy cows naturally infected with bovine leukemia virus exhibit abnormal B- and T-cell phenotypes after primary and secondary exposures to keyhole limpet hemocyanin. Front Vet Sci 4: 112. 32. Nobiron I, Thompson I, Brownlie J, Collins ME. 2000. Co-administration of IL-2 enhances antigen-specific immune responses following vaccination with DNA encoding the glycoprotein E2 of bovine viral diarrhoea virus. Vet Microbiol 76: 129–142. 22. Kwon S, Janssen CF, Velasquez FC, Zhang S, Aldrich MB, Shaitelman SF, DeSnyder SM, Sevick-Muraca EM. 2019. Radiation dose-dependent changes in lymphatic remodeling. Int J Radiat Oncol Biol Phys 105: 852–860. 14. Guzman E, Hope J, Taylor G, Smith AL, Cubillos-Zapata C, Charleston B. 2014. Bovine γδ T cells are a major regulatory T cell subset. J Immunol 193: 208–222. 20. Klapper JA, Downey SG, Smith FO, Yang JC, Hughes MS, Kammula US, Sherry RM, Royal RE, Steinberg SM, Rosenberg S. 2008. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma : a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer 113: 293–301. 39. Rochman Y, Spolski R, Leonard WJ. 2009. New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol 9: 480–490. 17. Hughes HP, Campos M, Godson DL, Van Drunen Littel-Van den Hurk S, McDougall L, Rapin N, Zamb T, Babiuk LA. 1991. Immunopotentiation of bovine herpes virus subunit vaccination by interleukin-2. Immunology 74: 461–466. 19. Jensen KD, Su X, Shin S, Li L, Youssef S, Yamasaki S, Steinman L, Saito T, Locksley RM, Davis MM, Baumgarth N, Chien YH. 2008. Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gamma. Immunity 29: 90–100. 45. Smith KA, Gillis S, Baker PE, McKenzie D, Ruscetti FW. 1979. T-cell growth factor-mediated T-cell proliferation. Ann N Y Acad Sci 332: 423–432. 13. Frie MC, Sporer KR, Wallace JC, Maes RK, Sordillo LM, Bartlett PC, Coussens PM. 2016. Reduced humoral immunity and atypical cell-mediated immunity in response to vaccination in cows naturally infected with bovine leukemia virus. Vet Immunol Immunopathol 182: 125–135. 31. Nakajima Y, Asano K, Mukai K, Urai T, Okuwa M, Sugama J, Nakatani T. 2018. Near-infrared fluorescence imaging directly visualizes lymphatic drainage pathways and connections between superficial and deep lymphatic systems in the mouse hindlimb. Sci Rep 8: 7078. 35. Pyeon D, Splitter GA. 1999. Regulation of bovine leukemia virus tax and pol mRNA levels by interleukin-2 and -10. J Virol 73: 8427–8434. 23. Krieg C, Létourneau S, Pantaleo G, Boyman O. 2010. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci USA 107: 11906–11911. 29. Mitra S, Ring AM, Amarnath S, Spangler JB, Li P, Ju W, Fischer S, Oh J, Spolski R, Weiskopf K, Kohrt H, Foley JE, Rajagopalan S, Long EO, Fowler DH, Waldmann TA, Garcia KC, Leonard WJ. 2015. Interleukin-2 activity can be fine tuned with engineered receptor signaling clamps. Immunity 42: 826–838. 47. Studer G, Tauriello G, Bienert S, Biasini M, Johner N, Schwede T. 2021. ProMod3-A versatile homology modelling toolbox. PLOS Comput Biol 17: e1008667. 51. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T. 2018. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46 W1: W296–W303. 9. Collins RA, Tayton HK, Gelder KI, Britton P, Oldham G. 1994. Cloning and expression of bovine and porcine interleukin-2 in baculovirus and analysis of species cross-reactivity. Vet Immunol Immunopathol 40: 313–324. 50. Wang X, Rickert M, Garcia KC. 2005. Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors. Science 310: 1159–1163. 46. Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA. 2006. Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor. Proc Natl Acad Sci USA 103: 2788–2793. 57. Zurawski SM, Vega F Jr, Doyle EL, Huyghe B, Flaherty K, McKay DB, Zurawski G. 1993. Definition and spatial location of mouse interleukin-2 residues that interact with its heterotrimeric receptor. EMBO J 12: 5113–5119. 37. Reddy DN, Reddy PG, Xue W, Minocha HC, Daley MJ, Blecha F. 1993. Immunopotentiation of bovine respiratory disease virus vaccines by interleukin-1 beta and interleukin-2. Vet Immunol Immunopathol 37: 25–38. 1. Akane K, Kojima S, Mak TW, Shiku H, Suzuki H. 2016. CD8+CD122+CD49dlow regulatory T cells maintain T-cell homeostasis by killing activated T cells via Fas/FasL-mediated cytotoxicity. Proc Natl Acad Sci USA 113: 2460–2465. 18. Izumi T, Kondo M, Takahashi T, Fujieda N, Kondo A, Tamura N, Murakawa T, Nakajima J, Matsushita H, Kakimi K. 2013. Ex vivo characterization of γδ T-cell repertoire in patients after adoptive transfer of Vγ9Vδ2 T cells expressing the interleukin-2 receptor β-chain and the common γ-chain. Cytotherapy 15: 481–491. 44. Smith FO, Downey SG, Klapper JA, Yang JC, Sherry RM, Royal RE, Kammula US, Hughes MS, Restifo NP, Levy CL, White DE, Steinberg SM, Rosenberg SA. 2008. Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin Cancer Res 14: 5610–5618. 26. Malek TR. 2008. The biology of interleukin-2. Annu Rev Immunol 26: 453–479. 43. Shimizu K, Ueda S, Kawamura M, Aoshima H, Satoh M, Nakabayashi J, Fujii SI. 2023. Combination of cancer vaccine with CD122-biased IL-2/anti-IL-2 Ab complex shapes the stem-like effector NK and CD8+ T cells against tumor. J Immunother Cancer 11: e006409. 3. Baldwin CL, Damani-Yokota P, Yirsaw A, Loonie K, Teixeira AF, Gillespie A. 2021. Special features of γδ T cells in ruminants. Mol Immunol 134: 161–169. 52. Weigel U, Meyer M, Sebald W. 1989. Mutant proteins of human interleukin 2. Renaturation yield, proliferative activity and receptor binding. Eur J Biochem 180: 295–300. 24. Krueger LA, Beitz DC, Humphrey SB, Stabel JR. 2016. Gamma delta T cells are early responders to Mycobacterium avium ssp. paratuberculosis in colostrum-replete Holstein calves. J Dairy Sci 99: 9040–9050. 54. Wyckoff JH 3rd, Howland JL, Scott CM, Smith RA, Confer AW. 2005. Recombinant bovine interleukin 2 enhances immunity and protection induced by Brucella abortus vaccines in cattle. Vet Microbiol 111: 77–87. 56. Zhang X, Sun S, Hwang I, Tough DF, Sprent J. 1998. Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 8: 591–599. 2. Arenas-Ramirez N, Woytschak J, Boyman O. 2015. Interleukin-2: Biology, Design and Application. Trends Immunol 36: 763–777. 6. Carmenate T, Pacios A, Enamorado M, Moreno E, Garcia-Martínez K, Fuente D, León K. 2013. Human IL-2 mutein with higher antitumor efficacy than wild type IL-2. J Immunol 190: 6230–6238. 21. Komatsu E, Nakajima Y, Mukai K, Urai T, Asano K, Okuwa M, Sugama J, Nakatani T. 2017. Lymph drainage during wound healing in a hindlimb lymphedema mouse model. Lymphat Res Biol 15: 32–38. 33. Ohira K, Nakahara A, Konnai S, Okagawa T, Nishimori A, Maekawa N, Ikebuchi R, Kohara J, Murata S, Ohashi K. 2016. Bovine leukemia virus reduces anti-viral cytokine activities and NK cytotoxicity by inducing TGF-β secretion from regulatory T cells. Immun Inflamm Dis 4: 52–63. 55. Zhang B, Sun J, Yuan Y, Ji D, Sun Y, Liu Y, Li S, Zhu X, Wu X, Hu J, Xie Q, Wu L, Liu L, Cheng B, Zhang Y, Jiang L, Zhao L, Yu F, Song W, Wang M, Xu Y, Ma S, Fei Y, Zhang L, Zhou D, Zhang X. 2023. Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity. Signal Transduct Target Ther 8: 28. 49. Tawfeeq MM, Tagawa M, Itoh Y, Sugimoto K, Kobayashi Y, Inokuma H. 2012. Overexpression of interleukin 2 receptor, thymidine kinase and immunoglobulin-associated alpha-1 messenger RNA in a clinical case of enzootic bovine leukosis. J Vet Med Sci 74: 1203–1206. 11. Derosa DC, Sordillo LM. 1997. Efficacy of a bovine Staphylococcus aureus vaccine using interleukin-2 as an adjuvant. Zentralbl Veterinärmed B 44: 599–607. 10. de Picciotto S, DeVita N, Hsiao CJ, Honan C, Tse SW, Nguyen M, Ferrari JD, Zheng W, Wipke BT, Huang E. 2022. Selective activation and expansion of regulatory T cells using lipid encapsulated mRNA encoding a long-acting IL-2 mutein. Nat Commun 13: 3866. 28. Mitoma S, El-Khaiat HM, Uto T, Sato K, Sekiguchi S, Norimine J. 2021. Characterization of bovine interleukin-2 stably expressed in HEK-293 cells. J Vet Med Sci 83: 134–141. 7. Casadesús AV, Cruz BM, Díaz W, González MÁ, Gómez T, Fernández B, González A, Ledón N, Sosa K, Castro K, López A, Plasencia C, Ramírez Y, Teillaud JL, Hernández C, León K, Hernández T. 2022. Potent immunomodulatory and antitumor effect of anti-CD20-IL2no-alpha tri-functional immunocytokine for cancer therapy. Front Immunol 13: 1021828. 27. McGill JL, Rusk RA, Guerra-Maupome M, Briggs RE, Sacco RE. 2016. Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with bovine RSV and mannheimia haemolytica. PLoS One 11: e0151083. 15. Harrell MI, Iritani BM, Ruddell A. 2008. Lymph node mapping in the mouse. J Immunol Methods 332: 170–174. 30. Mott HR, Baines BS, Hall RM, Cooke RM, Driscoll PC, Weir MP, Campbell ID. 1995. The solution structure of the F42A mutant of human interleukin 2. J Mol Biol 247: 979–994. 8. Casetti R, Agrati C, Wallace M, Sacchi A, Martini F, Martino A, Rinaldi A, Malkovsky M. 2009. Cutting edge: TGF-beta1 and IL-15 Induce FOXP3+ gammadelta regulatory T cells in the presence 44 45 46 47 48 49 50 51 52 53 10 54 11 55 12 56 13 57 14 15 16 17 18 19 1 2 3 4 5 6 7 8 9 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 |
References_xml | – reference: 30. Mott HR, Baines BS, Hall RM, Cooke RM, Driscoll PC, Weir MP, Campbell ID. 1995. The solution structure of the F42A mutant of human interleukin 2. J Mol Biol 247: 979–994. – reference: 54. Wyckoff JH 3rd, Howland JL, Scott CM, Smith RA, Confer AW. 2005. Recombinant bovine interleukin 2 enhances immunity and protection induced by Brucella abortus vaccines in cattle. Vet Microbiol 111: 77–87. – reference: 11. Derosa DC, Sordillo LM. 1997. Efficacy of a bovine Staphylococcus aureus vaccine using interleukin-2 as an adjuvant. Zentralbl Veterinärmed B 44: 599–607. – reference: 43. Shimizu K, Ueda S, Kawamura M, Aoshima H, Satoh M, Nakabayashi J, Fujii SI. 2023. Combination of cancer vaccine with CD122-biased IL-2/anti-IL-2 Ab complex shapes the stem-like effector NK and CD8+ T cells against tumor. J Immunother Cancer 11: e006409. – reference: 49. Tawfeeq MM, Tagawa M, Itoh Y, Sugimoto K, Kobayashi Y, Inokuma H. 2012. Overexpression of interleukin 2 receptor, thymidine kinase and immunoglobulin-associated alpha-1 messenger RNA in a clinical case of enzootic bovine leukosis. J Vet Med Sci 74: 1203–1206. – reference: 37. Reddy DN, Reddy PG, Xue W, Minocha HC, Daley MJ, Blecha F. 1993. Immunopotentiation of bovine respiratory disease virus vaccines by interleukin-1 beta and interleukin-2. Vet Immunol Immunopathol 37: 25–38. – reference: 33. Ohira K, Nakahara A, Konnai S, Okagawa T, Nishimori A, Maekawa N, Ikebuchi R, Kohara J, Murata S, Ohashi K. 2016. Bovine leukemia virus reduces anti-viral cytokine activities and NK cytotoxicity by inducing TGF-β secretion from regulatory T cells. Immun Inflamm Dis 4: 52–63. – reference: 13. Frie MC, Sporer KR, Wallace JC, Maes RK, Sordillo LM, Bartlett PC, Coussens PM. 2016. Reduced humoral immunity and atypical cell-mediated immunity in response to vaccination in cows naturally infected with bovine leukemia virus. Vet Immunol Immunopathol 182: 125–135. – reference: 2. Arenas-Ramirez N, Woytschak J, Boyman O. 2015. Interleukin-2: Biology, Design and Application. Trends Immunol 36: 763–777. – reference: 46. Stauber DJ, Debler EW, Horton PA, Smith KA, Wilson IA. 2006. Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor. Proc Natl Acad Sci USA 103: 2788–2793. – reference: 48. Taniguchi T, Minami Y. 1993. The IL-2/IL-2 receptor system: a current overview. Cell 73: 5–8. – reference: 20. Klapper JA, Downey SG, Smith FO, Yang JC, Hughes MS, Kammula US, Sherry RM, Royal RE, Steinberg SM, Rosenberg S. 2008. High-dose interleukin-2 for the treatment of metastatic renal cell carcinoma : a retrospective analysis of response and survival in patients treated in the surgery branch at the National Cancer Institute between 1986 and 2006. Cancer 113: 293–301. – reference: 14. Guzman E, Hope J, Taylor G, Smith AL, Cubillos-Zapata C, Charleston B. 2014. Bovine γδ T cells are a major regulatory T cell subset. J Immunol 193: 208–222. – reference: 56. Zhang X, Sun S, Hwang I, Tough DF, Sprent J. 1998. Potent and selective stimulation of memory-phenotype CD8+ T cells in vivo by IL-15. Immunity 8: 591–599. – reference: 6. Carmenate T, Pacios A, Enamorado M, Moreno E, Garcia-Martínez K, Fuente D, León K. 2013. Human IL-2 mutein with higher antitumor efficacy than wild type IL-2. J Immunol 190: 6230–6238. – reference: 25. Kobayashi M, Kojima K, Murayama K, Amano Y, Koyama T, Ogama N, Takeshita T, Fukuhara T, Tanaka N. 2021. MK-6, a novel not-α IL-2, elicits a potent antitumor activity by improving the effector to regulatory T cell balance. Cancer Sci 112: 4478–4489. – reference: 32. Nobiron I, Thompson I, Brownlie J, Collins ME. 2000. Co-administration of IL-2 enhances antigen-specific immune responses following vaccination with DNA encoding the glycoprotein E2 of bovine viral diarrhoea virus. Vet Microbiol 76: 129–142. – reference: 52. Weigel U, Meyer M, Sebald W. 1989. Mutant proteins of human interleukin 2. Renaturation yield, proliferative activity and receptor binding. Eur J Biochem 180: 295–300. – reference: 23. Krieg C, Létourneau S, Pantaleo G, Boyman O. 2010. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci USA 107: 11906–11911. – reference: 8. Casetti R, Agrati C, Wallace M, Sacchi A, Martini F, Martino A, Rinaldi A, Malkovsky M. 2009. Cutting edge: TGF-beta1 and IL-15 Induce FOXP3+ gammadelta regulatory T cells in the presence of antigen stimulation. J Immunol 183: 3574–3577. – reference: 45. Smith KA, Gillis S, Baker PE, McKenzie D, Ruscetti FW. 1979. T-cell growth factor-mediated T-cell proliferation. Ann N Y Acad Sci 332: 423–432. – reference: 39. Rochman Y, Spolski R, Leonard WJ. 2009. New insights into the regulation of T cells by gamma(c) family cytokines. Nat Rev Immunol 9: 480–490. – reference: 5. Carmenate T, Montalvo G, Lozada SL, Rodriguez Y, Ortiz Y, Díaz C, Avellanet J, Kim J, Surh CD, Graça L, León K. 2022. The antitumor effect induced by an IL-2 ‘no-alpha’ mutein depends on changes in the CD8+ T lymphocyte/Treg cell balance. Front Immunol 13: 974188. – reference: 15. Harrell MI, Iritani BM, Ruddell A. 2008. Lymph node mapping in the mouse. J Immunol Methods 332: 170–174. – reference: 7. Casadesús AV, Cruz BM, Díaz W, González MÁ, Gómez T, Fernández B, González A, Ledón N, Sosa K, Castro K, López A, Plasencia C, Ramírez Y, Teillaud JL, Hernández C, León K, Hernández T. 2022. Potent immunomodulatory and antitumor effect of anti-CD20-IL2no-alpha tri-functional immunocytokine for cancer therapy. Front Immunol 13: 1021828. – reference: 28. Mitoma S, El-Khaiat HM, Uto T, Sato K, Sekiguchi S, Norimine J. 2021. Characterization of bovine interleukin-2 stably expressed in HEK-293 cells. J Vet Med Sci 83: 134–141. – reference: 3. Baldwin CL, Damani-Yokota P, Yirsaw A, Loonie K, Teixeira AF, Gillespie A. 2021. Special features of γδ T cells in ruminants. Mol Immunol 134: 161–169. – reference: 50. Wang X, Rickert M, Garcia KC. 2005. Structure of the quaternary complex of interleukin-2 with its alpha, beta, and gammac receptors. Science 310: 1159–1163. – reference: 18. Izumi T, Kondo M, Takahashi T, Fujieda N, Kondo A, Tamura N, Murakawa T, Nakajima J, Matsushita H, Kakimi K. 2013. Ex vivo characterization of γδ T-cell repertoire in patients after adoptive transfer of Vγ9Vδ2 T cells expressing the interleukin-2 receptor β-chain and the common γ-chain. Cytotherapy 15: 481–491. – reference: 35. Pyeon D, Splitter GA. 1999. Regulation of bovine leukemia virus tax and pol mRNA levels by interleukin-2 and -10. J Virol 73: 8427–8434. – reference: 19. Jensen KD, Su X, Shin S, Li L, Youssef S, Yamasaki S, Steinman L, Saito T, Locksley RM, Davis MM, Baumgarth N, Chien YH. 2008. Thymic selection determines gammadelta T cell effector fate: antigen-naive cells make interleukin-17 and antigen-experienced cells make interferon gamma. Immunity 29: 90–100. – reference: 1. Akane K, Kojima S, Mak TW, Shiku H, Suzuki H. 2016. CD8+CD122+CD49dlow regulatory T cells maintain T-cell homeostasis by killing activated T cells via Fas/FasL-mediated cytotoxicity. Proc Natl Acad Sci USA 113: 2460–2465. – reference: 22. Kwon S, Janssen CF, Velasquez FC, Zhang S, Aldrich MB, Shaitelman SF, DeSnyder SM, Sevick-Muraca EM. 2019. Radiation dose-dependent changes in lymphatic remodeling. Int J Radiat Oncol Biol Phys 105: 852–860. – reference: 51. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T. 2018. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46 W1: W296–W303. – reference: 44. Smith FO, Downey SG, Klapper JA, Yang JC, Sherry RM, Royal RE, Kammula US, Hughes MS, Restifo NP, Levy CL, White DE, Steinberg SM, Rosenberg SA. 2008. Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin Cancer Res 14: 5610–5618. – reference: 12. Frie MC, Sporer KRB, Benitez OJ, Wallace JC, Droscha CJ, Bartlett PC, Coussens PM. 2017. Dairy cows naturally infected with bovine leukemia virus exhibit abnormal B- and T-cell phenotypes after primary and secondary exposures to keyhole limpet hemocyanin. Front Vet Sci 4: 112. – reference: 34. Onyshchenko K, Luo R, Guffart E, Gaedicke S, Grosu AL, Firat E, Niedermann G. 2023. Expansion of circulating stem-like CD8+ T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice. Nat Commun 14: 2087. – reference: 55. Zhang B, Sun J, Yuan Y, Ji D, Sun Y, Liu Y, Li S, Zhu X, Wu X, Hu J, Xie Q, Wu L, Liu L, Cheng B, Zhang Y, Jiang L, Zhao L, Yu F, Song W, Wang M, Xu Y, Ma S, Fei Y, Zhang L, Zhou D, Zhang X. 2023. Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity. Signal Transduct Target Ther 8: 28. – reference: 4. Bertoni M, Kiefer F, Biasini M, Bordoli L, Schwede T. 2017. Modeling protein quaternary structure of homo- and hetero-oligomers beyond binary interactions by homology. Sci Rep 7: 10480. – reference: 47. Studer G, Tauriello G, Bienert S, Biasini M, Johner N, Schwede T. 2021. ProMod3-A versatile homology modelling toolbox. PLOS Comput Biol 17: e1008667. – reference: 53. Wrenshall LE, Clabaugh SE, Cool DR, Arumugam P, Grunwald WC, Smith DR, Liu GC, Miller JD. 2014. Identification of a cytotoxic form of dimeric interleukin-2 in murine tissues. PLoS One 9: e102191. – reference: 26. Malek TR. 2008. The biology of interleukin-2. Annu Rev Immunol 26: 453–479. – reference: 29. Mitra S, Ring AM, Amarnath S, Spangler JB, Li P, Ju W, Fischer S, Oh J, Spolski R, Weiskopf K, Kohrt H, Foley JE, Rajagopalan S, Long EO, Fowler DH, Waldmann TA, Garcia KC, Leonard WJ. 2015. Interleukin-2 activity can be fine tuned with engineered receptor signaling clamps. Immunity 42: 826–838. – reference: 38. Ren J, Chu AE, Jude KM, Picton LK, Kare AJ, Su L, Montano Romero A, Huang PS, Garcia KC. 2022. Interleukin-2 superkines by computational design. Proc Natl Acad Sci USA 119: e2117401119. – reference: 16. Honda Y, Waithaka M, Taracha EL, Duchateau L, Musoke AJ, McKeever DJ. 1998. Delivery of the Theileria parva p67 antigen to cattle using recombinant vaccinia virus: IL-2 enhances protection. Vaccine 16: 1276–1282. – reference: 31. Nakajima Y, Asano K, Mukai K, Urai T, Okuwa M, Sugama J, Nakatani T. 2018. Near-infrared fluorescence imaging directly visualizes lymphatic drainage pathways and connections between superficial and deep lymphatic systems in the mouse hindlimb. Sci Rep 8: 7078. – reference: 10. de Picciotto S, DeVita N, Hsiao CJ, Honan C, Tse SW, Nguyen M, Ferrari JD, Zheng W, Wipke BT, Huang E. 2022. Selective activation and expansion of regulatory T cells using lipid encapsulated mRNA encoding a long-acting IL-2 mutein. Nat Commun 13: 3866. – reference: 17. Hughes HP, Campos M, Godson DL, Van Drunen Littel-Van den Hurk S, McDougall L, Rapin N, Zamb T, Babiuk LA. 1991. Immunopotentiation of bovine herpes virus subunit vaccination by interleukin-2. Immunology 74: 461–466. – reference: 21. Komatsu E, Nakajima Y, Mukai K, Urai T, Asano K, Okuwa M, Sugama J, Nakatani T. 2017. Lymph drainage during wound healing in a hindlimb lymphedema mouse model. Lymphat Res Biol 15: 32–38. – reference: 9. Collins RA, Tayton HK, Gelder KI, Britton P, Oldham G. 1994. Cloning and expression of bovine and porcine interleukin-2 in baculovirus and analysis of species cross-reactivity. Vet Immunol Immunopathol 40: 313–324. – reference: 40. Rogers AN, Vanburen DG, Hedblom EE, Tilahun ME, Telfer JC, Baldwin CL. 2005. Gammadelta T cell function varies with the expressed WC1 coreceptor. J Immunol 174: 3386–3393. – reference: 27. McGill JL, Rusk RA, Guerra-Maupome M, Briggs RE, Sacco RE. 2016. Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with bovine RSV and mannheimia haemolytica. PLoS One 11: e0151083. – reference: 41. Sauvé K, Nachman M, Spence C, Bailon P, Campbell E, Tsien WH, Kondas JA, Hakimi J, Ju G. 1991. Localization in human interleukin 2 of the binding site to the alpha chain (p55) of the interleukin 2 receptor. Proc Natl Acad Sci USA 88: 4636–4640. – reference: 36. Reddy PG, Blecha F, Minocha HC, Anderson GA, Morrill JL, Fedorka-Cray PJ, Baker PE. 1989. Bovine recombinant interleukin-2 augments immunity and resistance to bovine herpesvirus infection. Vet Immunol Immunopathol 23: 61–74. – reference: 57. Zurawski SM, Vega F Jr, Doyle EL, Huyghe B, Flaherty K, McKay DB, Zurawski G. 1993. Definition and spatial location of mouse interleukin-2 residues that interact with its heterotrimeric receptor. EMBO J 12: 5113–5119. – reference: 42. Shibata K, Yamada H, Nakamura R, Sun X, Itsumi M, Yoshikai Y. 2008. Identification of CD25+ gamma delta T cells as fetal thymus-derived naturally occurring IL-17 producers. J Immunol 181: 5940–5947. – reference: 24. Krueger LA, Beitz DC, Humphrey SB, Stabel JR. 2016. Gamma delta T cells are early responders to Mycobacterium avium ssp. paratuberculosis in colostrum-replete Holstein calves. J Dairy Sci 99: 9040–9050. – ident: 51 doi: 10.1093/nar/gky427 – ident: 30 doi: 10.1006/jmbi.1994.0194 – ident: 32 doi: 10.1016/S0378-1135(00)00238-8 – ident: 14 doi: 10.4049/jimmunol.1303398 – ident: 39 doi: 10.1038/nri2580 – ident: 49 doi: 10.1292/jvms.12-0100 – ident: 56 doi: 10.1016/S1074-7613(00)80564-6 – ident: 5 doi: 10.3389/fimmu.2022.974188 – ident: 29 doi: 10.1016/j.immuni.2015.04.018 – ident: 46 doi: 10.1073/pnas.0511161103 – ident: 43 doi: 10.1136/jitc-2022-006409 – ident: 41 doi: 10.1073/pnas.88.11.4636 – ident: 47 doi: 10.1371/journal.pcbi.1008667 – ident: 54 doi: 10.1016/j.vetmic.2005.09.004 – ident: 12 doi: 10.3389/fvets.2017.00112 – ident: 53 doi: 10.1371/journal.pone.0102191 – ident: 1 doi: 10.1073/pnas.1525098113 – ident: 22 doi: 10.1016/j.ijrobp.2019.07.054 – ident: 23 doi: 10.1073/pnas.1002569107 – ident: 25 doi: 10.1111/cas.15127 – ident: 17 – ident: 11 doi: 10.1111/j.1439-0450.1997.tb01013.x – ident: 20 doi: 10.1002/cncr.23552 – ident: 4 doi: 10.1038/s41598-017-09654-8 – ident: 7 doi: 10.3389/fimmu.2022.1021828 – ident: 34 doi: 10.1038/s41467-023-37825-x – ident: 10 doi: 10.1038/s41467-022-31130-9 – ident: 6 doi: 10.4049/jimmunol.1201895 – ident: 42 doi: 10.4049/jimmunol.181.9.5940 – ident: 3 doi: 10.1016/j.molimm.2021.02.028 – ident: 35 doi: 10.1128/JVI.73.10.8427-8434.1999 – ident: 9 doi: 10.1016/0165-2427(94)90042-6 – ident: 44 doi: 10.1158/1078-0432.CCR-08-0116 – ident: 13 doi: 10.1016/j.vetimm.2016.10.013 – ident: 45 doi: 10.1111/j.1749-6632.1979.tb47136.x – ident: 18 doi: 10.1016/j.jcyt.2012.12.004 – ident: 2 doi: 10.1016/j.it.2015.10.003 – ident: 15 doi: 10.1016/j.jim.2007.11.012 – ident: 31 doi: 10.1038/s41598-018-25383-y – ident: 26 doi: 10.1146/annurev.immunol.26.021607.090357 – ident: 40 doi: 10.4049/jimmunol.174.6.3386 – ident: 57 doi: 10.1002/j.1460-2075.1993.tb06206.x – ident: 19 doi: 10.1016/j.immuni.2008.04.022 – ident: 33 doi: 10.1002/iid3.93 – ident: 27 doi: 10.1371/journal.pone.0151083 – ident: 21 doi: 10.1089/lrb.2016.0026 – ident: 55 doi: 10.1038/s41392-022-01208-3 – ident: 8 doi: 10.4049/jimmunol.0901334 – ident: 37 doi: 10.1016/0165-2427(93)90013-T – ident: 28 doi: 10.1292/jvms.20-0423 – ident: 50 doi: 10.1126/science.1117893 – ident: 52 doi: 10.1111/j.1432-1033.1989.tb14647.x – ident: 24 doi: 10.3168/jds.2016-11144 – ident: 38 doi: 10.1073/pnas.2117401119 – ident: 16 doi: 10.1016/S0264-410X(98)00041-3 – ident: 36 doi: 10.1016/0165-2427(89)90110-4 – ident: 48 doi: 10.1016/0092-8674(93)90152-G |
SSID | ssj0021469 |
Score | 2.3807466 |
Snippet | Delivery of engineered interleukin-2 (IL-2) variants (muteins) is thought to be a promising cancer therapy in humans and mice. Our previous study indicated... |
SourceID | pubmedcentral proquest pubmed crossref jstage |
SourceType | Open Access Repository Aggregation Database Index Database Publisher |
StartPage | 781 |
SubjectTerms | Animals bovine interleukin-2 Cancer therapies Cattle CD122 CD122 antigen CD25 antigen CD4 antigen CD4-Positive T-Lymphocytes - drug effects CD8 antigen Cell surface Cytokines Immunology Interleukin 2 Interleukin-2 - genetics Interleukin-2 - pharmacology Killer Cells, Natural - drug effects Killer Cells, Natural - immunology Leukocytes (mononuclear) Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - immunology Lymphocytes Lymphocytes T mutein natural killer cell Natural killer cells Peripheral blood mononuclear cells selective stimulation Signal transduction |
Title | Selectivity of bovine interleukin-2 mutein stimulation on bovine peripheral blood mononuclear cells |
URI | https://www.jstage.jst.go.jp/article/jvms/87/7/87_24-0470/_article/-char/en https://www.ncbi.nlm.nih.gov/pubmed/40451851 https://www.proquest.com/docview/3239609615 https://www.proquest.com/docview/3214725139 https://pubmed.ncbi.nlm.nih.gov/PMC12246588 |
Volume | 87 |
hasFullText | 1 |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
ispartofPNX | Journal of Veterinary Medical Science, 2025, Vol.87(7), pp.781-790 |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3daxQxEB9KFemL1Pq1bS0R9DF1L8luskgpIpaqnC960rcl2WS19W7P3ofof-9M9gOv9ElYFpbMsktmhsxkJr8fwIsiSONz77m2QnKVu5SbUHsui2CC0sIKQYeTx5_y84n6cJFdbEHPNtpN4PLW1I74pCaL6fHv6z-n6PAnERuhEK-ufs2Wx4L6KTQm73dwTdLEZTBWQz2B2Ktb1L1RzjWu-l0L_M23d-CeIsAVk4021qm7VxiqfQu3RaE3myn_WZ3OduF-F1ayN60dPICt0OzB3lfqdYkHbtm4q6E_hOpzpL6JpBFsXjNHewqBEW7EYhrWPy4bLthsTSyYDP1_1vF7Mbw6UQJHjmgEUxb73hma8rwhYGS7YFQJWD6Cydm7L2_PeUe1wKusMCseMh2CVqkJla1rlXlVF0b4tCpSEYz0VeExr3HOVbXMndFSpk4bZbXy-IASj2EbvxSeAlNCBaMx77XWKi-s85V1udCuzkywtkrgZT-x5c8WUaOkTAR1UZIuSqFK0kUCr9tZH6Q6X2qljC413TrpYZAOq6HHJ3DYq6rsjaqUQhLAHgZxCTwfhtGfaGpsE-ZrkhmhiWYYGCfwpNXs8AO9bSRgNnQ-CBBW9-ZIc_k9YnZTARODPbP__68ewI4g8uG4_3MI26vFOjzDiGjljjAXeP_xKJr8XwVrEcM |
linkProvider | Scholars Portal |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Selectivity+of+bovine+interleukin-2+mutein+stimulation+on+bovine+peripheral+blood+mononuclear+cells&rft.jtitle=Journal+of+veterinary+medical+science&rft.au=MITOMA%2C+Shuya&rft.au=UTO%2C+Tomofumi&rft.au=FUKAYA%2C+Tomohiro&rft.au=TOMINAGA%2C+Moe&rft.date=2025&rft.pub=The+Japanese+Society+of+Veterinary+Science&rft.issn=0916-7250&rft.eissn=1347-7439&rft.volume=87&rft.issue=7&rft.spage=781&rft.epage=790&rft_id=info:doi/10.1292%2Fjvms.24-0470&rft_id=info%3Apmid%2F40451851&rft.externalDocID=PMC12246588 |
thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0916-7250&client=summon |
thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0916-7250&client=summon |
thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0916-7250&client=summon |