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...

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Published inJournal of Veterinary Medical Science Vol. 87; no. 7; pp. 781 - 790
Main Authors MITOMA, Shuya, UTO, Tomofumi, FUKAYA, Tomohiro, TOMINAGA, Moe, SEKIGUCHI, Satoshi, SATO, Katsuaki, NORIMINE, Junzo
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Published Japan JAPANESE SOCIETY OF VETERINARY SCIENCE 2025
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The Japanese Society of Veterinary Science
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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
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  fullname: UTO, Tomofumi
  organization: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
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  fullname: FUKAYA, Tomohiro
  organization: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
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  fullname: TOMINAGA, Moe
  organization: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan
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  fullname: SEKIGUCHI, Satoshi
  organization: Department of Veterinary Sciences, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan
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  organization: Center for Animal Disease Control, University of Miyazaki, Miyazaki, Japan
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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
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Keywords bovine interleukin-2
mutein
selective stimulation
natural killer cell
CD122
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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
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45
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50
51
52
53
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54
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9
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22
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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
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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...
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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
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https://pubmed.ncbi.nlm.nih.gov/PMC12246588
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