Rapamycin/IL-2 Combination Therapy in Patients With Type 1 Diabetes Augments Tregs yet Transiently Impairs β-Cell Function

Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 m...

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Published in	Diabetes (New York, N.Y.) Vol. 61; no. 9; pp. 2340 - 2348
Main Authors	Long, S. Alice, Rieck, Mary, Sanda, Srinath, Bollyky, Jennifer B., Samuels, Peter L., Goland, Robin, Ahmann, Andrew, Rabinovitch, Alex, Aggarwal, Sudeepta, Phippard, Deborah, Turka, Laurence A., Ehlers, Mario R., Bianchine, Peter J., Boyle, Karen D., Adah, Steven A., Bluestone, Jeffrey A., Buckner, Jane H., Greenbaum, Carla J.
Format	Journal Article
Language	English
Published	Alexandria, VA American Diabetes Association 01.09.2012
Subjects	Animals Biological and medical sciences Diabetes Mellitus, Type 1 - drug therapy Diabetes Mellitus, Type 1 - immunology Diabetes. Impaired glucose tolerance Dosage and administration Drug therapy Drug Therapy, Combination Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Humans Immunology and Transplantation Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - physiology Interleukin-2 Interleukin-2 - administration & dosage Interleukin-2 - therapeutic use Medical sciences Mice Mice, Inbred NOD Rapamycin Sirolimus Sirolimus - administration & dosage T-Lymphocytes, Regulatory - immunology Type 1 diabetes Endocrinopathy Human Immunopathology Interleukin 2 Type 1 diabetes Cytokine Langerhans islet Autoimmune disease β Cell Endocrine pancreas
Online Access	Get full text
ISSN	0012-1797 1939-327X 1939-327X
DOI	10.2337/db12-0049

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Abstract	Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 × 10(6) IU IL-2 s.c. three times per week for 1 month. β-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural killer cells and eosinophils occurred with IL-2 therapy. Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient β-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy.
AbstractList	Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 × 10(6) IU IL-2 s.c. three times per week for 1 month. β-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural killer cells and eosinophils occurred with IL-2 therapy. Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient β-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy.Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 × 10(6) IU IL-2 s.c. three times per week for 1 month. β-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural killer cells and eosinophils occurred with IL-2 therapy. Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient β-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy. Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/ IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 x [10.sup.6] IU IL-2 s.c. three times per week for 1 month. β-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural loller cells and eosinophils occurred with IL-2 therapy. Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient β-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy. Diabetes 61:2340-2348, 2012 Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the safety and immunologic effects of rapamycin/IL-2 combination therapy in type 1 diabetic (T1D) patients. Nine T1D subjects were treated with 2-4 mg/day rapamycin orally for 3 months and 4.5 × 10(6) IU IL-2 s.c. three times per week for 1 month. β-Cell function was monitored by measuring C-peptide. Immunologic changes were monitored using flow cytometry and serum analyses. Regulatory T cells (Tregs) increased within the first month of therapy, yet clinical and metabolic data demonstrated a transient worsening in all subjects. The increase in Tregs was transient, paralleling IL-2 treatment, whereas the response of Tregs to IL-2, as measured by STAT5 phosphorylation, increased and persisted after treatment. No differences were observed in effector T-cell subset frequencies, but an increase in natural killer cells and eosinophils occurred with IL-2 therapy. Rapamycin/IL-2 therapy, as given in this phase 1 study, resulted in transient β-cell dysfunction despite an increase in Tregs. Such results highlight the difficulties in translating therapies to the clinic and emphasize the importance of broadly interrogating the immune system to evaluate the effects of therapy.
Audience	Professional
Author	Buckner, Jane H. Long, S. Alice Greenbaum, Carla J. Adah, Steven A. Bluestone, Jeffrey A. Aggarwal, Sudeepta Rieck, Mary Turka, Laurence A. Goland, Robin Ahmann, Andrew Rabinovitch, Alex Bianchine, Peter J. Samuels, Peter L. Bollyky, Jennifer B. Ehlers, Mario R. Boyle, Karen D. Sanda, Srinath Phippard, Deborah
Author_xml	– sequence: 1 givenname: S. Alice surname: Long fullname: Long, S. Alice organization: Translational Immunology Program, Benaroya Research Institute, Seattle, Washington – sequence: 2 givenname: Mary surname: Rieck fullname: Rieck, Mary organization: Translational Immunology Program, Benaroya Research Institute, Seattle, Washington – sequence: 3 givenname: Srinath surname: Sanda fullname: Sanda, Srinath organization: Diabetes Program, Benaroya Research Institute, Seattle, Washington – sequence: 4 givenname: Jennifer B. surname: Bollyky fullname: Bollyky, Jennifer B. organization: Diabetes Program, Benaroya Research Institute, Seattle, Washington – sequence: 5 givenname: Peter L. surname: Samuels fullname: Samuels, Peter L. organization: Translational Immunology Program, Benaroya Research Institute, Seattle, Washington – sequence: 6 givenname: Robin surname: Goland fullname: Goland, Robin organization: Naomi Berrie Diabetes Center, Columbia University Medical Center, New York, New York – sequence: 7 givenname: Andrew surname: Ahmann fullname: Ahmann, Andrew organization: Harold Schnitzer Diabetes Health Center, Oregon Health and Science University, Portland, Oregon – sequence: 8 givenname: Alex surname: Rabinovitch fullname: Rabinovitch, Alex organization: Sanford Research, University of South Dakota, Sioux Falls, South Dakota – sequence: 9 givenname: Sudeepta surname: Aggarwal fullname: Aggarwal, Sudeepta organization: Tolerance Assays and Data Analysis Group, Immune Tolerance Network, Bethesda, Maryland – sequence: 10 givenname: Deborah surname: Phippard fullname: Phippard, Deborah organization: Tolerance Assays and Data Analysis Group, Immune Tolerance Network, Bethesda, Maryland – sequence: 11 givenname: Laurence A. surname: Turka fullname: Turka, Laurence A. organization: Tolerance Assays and Data Analysis Group, Immune Tolerance Network, Bethesda, Maryland, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts – sequence: 12 givenname: Mario R. surname: Ehlers fullname: Ehlers, Mario R. organization: Clinical Trials Group, Immune Tolerance Network, San Francisco, California – sequence: 13 givenname: Peter J. surname: Bianchine fullname: Bianchine, Peter J. organization: Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland – sequence: 14 givenname: Karen D. surname: Boyle fullname: Boyle, Karen D. organization: Rho Federal Systems Division, Inc., Chapel Hill, North Carolina – sequence: 15 givenname: Steven A. surname: Adah fullname: Adah, Steven A. organization: Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland – sequence: 16 givenname: Jeffrey A. surname: Bluestone fullname: Bluestone, Jeffrey A. organization: Diabetes Center and Department of Medicine, University of California San Francisco, San Francisco, California – sequence: 17 givenname: Jane H. surname: Buckner fullname: Buckner, Jane H. organization: Translational Immunology Program, Benaroya Research Institute, Seattle, Washington – sequence: 18 givenname: Carla J. surname: Greenbaum fullname: Greenbaum, Carla J. organization: Diabetes Program, Benaroya Research Institute, Seattle, Washington
BackLink	http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26369751$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/22721971$$D View this record in MEDLINE/PubMed
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Cites_doi	10.1007/s00125-010-1959-6 10.2337/db06-0173 10.1146/annurev.immunol.26.021607.090357 10.1016/j.immuni.2008.03.016 10.1056/NEJMoa012864 10.1111/j.1365-2567.2010.03360.x 10.1016/S0140-6736(11)60931-8 10.1182/blood-2009-10-251488 10.2741/2773 10.2337/dc09-1349 10.1016/j.immuni.2009.04.014 10.1016/S0140-6736(11)60886-6 10.1084/jem.20100209 10.2337/db09-0694 10.2337/diab.45.7.926 10.4161/epi.6.2.13755 10.1038/nri2889 10.1172/JCI44862 10.1016/j.autrev.2008.04.008 10.2337/diabetes.51.3.638 10.1681/ASN.2006030196 10.1073/pnas.0705863104 10.2337/dc07-2451 10.1158/1078-0432.CCR-06-1159 10.4049/jimmunol.182.3.1541 10.1056/NEJMoa0904452 10.4049/jimmunol.139.3.855 10.2337/db08-0138 10.1073/pnas.0601335103 10.2337/db11-1213 10.4049/jimmunol.0804358 10.1158/0008-5472.CAN-08-2361 10.1016/j.transproceed.2008.10.032 10.1182/blood.V86.9.3287.bloodjournal8693287 10.1038/nri2546 10.1038/nri2474 10.1056/NEJMoa043980 10.1038/ni.2005 10.1016/S0140-6736(11)60895-7 10.1006/cimm.2001.1808 10.1056/NEJMoa1108188 10.1056/NEJMoa1105143 10.1016/j.immuni.2010.09.002
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Keywords	Endocrinopathy Human Immunopathology Interleukin 2 Type 1 diabetes Cytokine Langerhans islet Autoimmune disease β Cell Endocrine pancreas
Language	English
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References	Robb (2022031209251281700_B42) 1987; 139 Piemonti (2022031209251281700_B32) 2011; 54 Thomson (2022031209251281700_B7) 2009; 9 Long (2022031209251281700_B23) 2010; 59 Rabinovitch (2022031209251281700_B20) 2002; 51 Orban (2022031209251281700_B3) 2011; 378 Di Paolo (2022031209251281700_B33) 2006; 17 Maier (2022031209251281700_B43) 2009; 182 Verge (2022031209251281700_B22) 1996; 45 Huehn (2022031209251281700_B29) 2009; 9 Tanemura (2022031209251281700_B30) 2009; 41 Turnquist (2022031209251281700_B41) 2010; 115 Turka (2022031209251281700_B13) 2008; 13 Koulmanda (2022031209251281700_B16) 2007; 104 Sehouli (2022031209251281700_B25) 2011; 6 Koreth (2022031209251281700_B18) 2011; 365 Schleinitz (2022031209251281700_B35) 2010; 131 Keymeulen (2022031209251281700_B2) 2005; 352 Saadoun (2022031209251281700_B19) 2011; 365 Delgoffe (2022031209251281700_B9) 2011; 12 Malek (2022031209251281700_B12) 2008; 26 Grinberg-Bleyer (2022031209251281700_B15) 2010; 207 Greenbaum (2022031209251281700_B21) 2008; 31 Buckner (2022031209251281700_B5) 2010; 10 Herold (2022031209251281700_B1) 2002; 346 Delgoffe (2022031209251281700_B8) 2009; 30 Hulme (2022031209251281700_B14) 2012; 61 Pescovitz (2022031209251281700_B4) 2009; 361 Monti (2022031209251281700_B11) 2008; 57 Wieczorek (2022031209251281700_B24) 2009; 69 Knip (2022031209251281700_B6) 2008; 7 Orange (2022031209251281700_B40) 2011; 121 Hoenstein (2022031209251281700_B38) 2001; 210 Powell (2022031209251281700_B10) 2010; 33 Wherrett (2022031209251281700_B28) 2011; 378 Varker (2022031209251281700_B39) 2006; 12 Zhang (2022031209251281700_B31) 2006; 55 Gottlieb (2022031209251281700_B26) 2010; 33 Bernstein (2022031209251281700_B37) 1995; 86 Brauner (2022031209251281700_B34) 2010; 184 Bielekova (2022031209251281700_B36) 2006; 103 Tang (2022031209251281700_B17) 2008; 28 Sherry (2022031209251281700_B27) 2011; 378 22923646 - Diabetes. 2012 Sep;61(9):2214-5
References_xml	– volume: 54 start-page: 433 year: 2011 ident: 2022031209251281700_B32 article-title: Beta cell function during rapamycin monotherapy in long-term type 1 diabetes publication-title: Diabetologia doi: 10.1007/s00125-010-1959-6 – volume: 55 start-page: 2429 year: 2006 ident: 2022031209251281700_B31 article-title: Sirolimus is associated with reduced islet engraftment and impaired beta-cell function publication-title: Diabetes doi: 10.2337/db06-0173 – volume: 26 start-page: 453 year: 2008 ident: 2022031209251281700_B12 article-title: The biology of interleukin-2 publication-title: Annu Rev Immunol doi: 10.1146/annurev.immunol.26.021607.090357 – volume: 28 start-page: 687 year: 2008 ident: 2022031209251281700_B17 article-title: Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction publication-title: Immunity doi: 10.1016/j.immuni.2008.03.016 – volume: 346 start-page: 1692 year: 2002 ident: 2022031209251281700_B1 article-title: Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus publication-title: N Engl J Med doi: 10.1056/NEJMoa012864 – volume: 131 start-page: 451 year: 2010 ident: 2022031209251281700_B35 article-title: Natural killer cells in human autoimmune diseases publication-title: Immunology doi: 10.1111/j.1365-2567.2010.03360.x – volume: 378 start-page: 487 year: 2011 ident: 2022031209251281700_B27 article-title: Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial publication-title: Lancet doi: 10.1016/S0140-6736(11)60931-8 – volume: 115 start-page: 4758 year: 2010 ident: 2022031209251281700_B41 article-title: mTOR and GSK-3 shape the CD4+ T-cell stimulatory and differentiation capacity of myeloid DCs after exposure to LPS publication-title: Blood doi: 10.1182/blood-2009-10-251488 – volume: 13 start-page: 1440 year: 2008 ident: 2022031209251281700_B13 article-title: IL-2 signaling and CD4+ CD25+ Foxp3+ regulatory T cells publication-title: Front Biosci doi: 10.2741/2773 – volume: 33 start-page: 826 year: 2010 ident: 2022031209251281700_B26 article-title: Failure to preserve beta-cell function with mycophenolate mofetil and daclizumab combined therapy in patients with new-onset type 1 diabetes publication-title: Diabetes Care doi: 10.2337/dc09-1349 – volume: 30 start-page: 832 year: 2009 ident: 2022031209251281700_B8 article-title: The mTOR kinase differentially regulates effector and regulatory T cell lineage commitment publication-title: Immunity doi: 10.1016/j.immuni.2009.04.014 – volume: 378 start-page: 412 year: 2011 ident: 2022031209251281700_B3 article-title: Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial publication-title: Lancet doi: 10.1016/S0140-6736(11)60886-6 – volume: 207 start-page: 1871 year: 2010 ident: 2022031209251281700_B15 article-title: IL-2 reverses established type 1 diabetes in NOD mice by a local effect on pancreatic regulatory T cells publication-title: J Exp Med doi: 10.1084/jem.20100209 – volume: 59 start-page: 407 year: 2010 ident: 2022031209251281700_B23 article-title: Defects in IL-2R signaling contribute to diminished maintenance of FOXP3 expression in CD4(+)CD25(+) regulatory T-cells of type 1 diabetic subjects publication-title: Diabetes doi: 10.2337/db09-0694 – volume: 45 start-page: 926 year: 1996 ident: 2022031209251281700_B22 article-title: Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies publication-title: Diabetes doi: 10.2337/diab.45.7.926 – volume: 6 start-page: 236 year: 2011 ident: 2022031209251281700_B25 article-title: Epigenetic quantification of tumor-infiltrating T-lymphocytes publication-title: Epigenetics doi: 10.4161/epi.6.2.13755 – volume: 10 start-page: 849 year: 2010 ident: 2022031209251281700_B5 article-title: Mechanisms of impaired regulation by CD4(+)CD25(+)FOXP3(+) regulatory T cells in human autoimmune diseases publication-title: Nat Rev Immunol doi: 10.1038/nri2889 – volume: 121 start-page: 1535 year: 2011 ident: 2022031209251281700_B40 article-title: IL-2 induces a WAVE2-dependent pathway for actin reorganization that enables WASp-independent human NK cell function publication-title: J Clin Invest doi: 10.1172/JCI44862 – volume: 7 start-page: 550 year: 2008 ident: 2022031209251281700_B6 article-title: Autoimmune mechanisms in type 1 diabetes publication-title: Autoimmun Rev doi: 10.1016/j.autrev.2008.04.008 – volume: 51 start-page: 638 year: 2002 ident: 2022031209251281700_B20 article-title: Combination therapy with sirolimus and interleukin-2 prevents spontaneous and recurrent autoimmune diabetes in NOD mice publication-title: Diabetes doi: 10.2337/diabetes.51.3.638 – volume: 17 start-page: 2236 year: 2006 ident: 2022031209251281700_B33 article-title: Chronic inhibition of mammalian target of rapamycin signaling downregulates insulin receptor substrates 1 and 2 and AKT activation: a crossroad between cancer and diabetes? publication-title: J Am Soc Nephrol doi: 10.1681/ASN.2006030196 – volume: 104 start-page: 13074 year: 2007 ident: 2022031209251281700_B16 article-title: Modification of adverse inflammation is required to cure new-onset type 1 diabetic hosts publication-title: Proc Natl Acad Sci USA doi: 10.1073/pnas.0705863104 – volume: 31 start-page: 1966 year: 2008 ident: 2022031209251281700_B21 article-title: Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes publication-title: Diabetes Care doi: 10.2337/dc07-2451 – volume: 12 start-page: 5850 year: 2006 ident: 2022031209251281700_B39 article-title: Multiparametric flow cytometric analysis of signal transducer and activator of transcription 5 phosphorylation in immune cell subsets in vitro and following interleukin-2 immunotherapy publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-06-1159 – volume: 182 start-page: 1541 year: 2009 ident: 2022031209251281700_B43 article-title: Soluble IL-2RA levels in multiple sclerosis subjects and the effect of soluble IL-2RA on immune responses publication-title: J Immunol doi: 10.4049/jimmunol.182.3.1541 – volume: 361 start-page: 2143 year: 2009 ident: 2022031209251281700_B4 article-title: Rituximab, B-lymphocyte depletion, and preservation of beta-cell function publication-title: N Engl J Med doi: 10.1056/NEJMoa0904452 – volume: 139 start-page: 855 year: 1987 ident: 2022031209251281700_B42 article-title: Structure-function relationships for the IL 2-receptor system. IV. Analysis of the sequence and ligand-binding properties of soluble Tac protein publication-title: J Immunol doi: 10.4049/jimmunol.139.3.855 – volume: 57 start-page: 2341 year: 2008 ident: 2022031209251281700_B11 article-title: Rapamycin monotherapy in patients with type 1 diabetes modifies CD4+CD25+FOXP3+ regulatory T-cells publication-title: Diabetes doi: 10.2337/db08-0138 – volume: 103 start-page: 5941 year: 2006 ident: 2022031209251281700_B36 article-title: Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2Ralpha-targeted therapy (daclizumab) in multiple sclerosis publication-title: Proc Natl Acad Sci USA doi: 10.1073/pnas.0601335103 – volume: 61 start-page: 14 year: 2012 ident: 2022031209251281700_B14 article-title: Central role for interleukin-2 in type 1 diabetes publication-title: Diabetes doi: 10.2337/db11-1213 – volume: 184 start-page: 2272 year: 2010 ident: 2022031209251281700_B34 article-title: Distinct phenotype and function of NK cells in the pancreas of nonobese diabetic mice publication-title: J Immunol doi: 10.4049/jimmunol.0804358 – volume: 69 start-page: 599 year: 2009 ident: 2022031209251281700_B24 article-title: Quantitative DNA methylation analysis of FOXP3 as a new method for counting regulatory T cells in peripheral blood and solid tissue publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-08-2361 – volume: 41 start-page: 334 year: 2009 ident: 2022031209251281700_B30 article-title: Rapamycin induces autophagy in islets: relevance in islet transplantation publication-title: Transplant Proc doi: 10.1016/j.transproceed.2008.10.032 – volume: 86 start-page: 3287 year: 1995 ident: 2022031209251281700_B37 article-title: Prolonged administration of low-dose interleukin-2 in human immunodeficiency virus-associated malignancy results in selective expansion of innate immune effectors without significant clinical toxicity publication-title: Blood doi: 10.1182/blood.V86.9.3287.bloodjournal8693287 – volume: 9 start-page: 324 year: 2009 ident: 2022031209251281700_B7 article-title: Immunoregulatory functions of mTOR inhibition publication-title: Nat Rev Immunol doi: 10.1038/nri2546 – volume: 9 start-page: 83 year: 2009 ident: 2022031209251281700_B29 article-title: Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? publication-title: Nat Rev Immunol doi: 10.1038/nri2474 – volume: 352 start-page: 2598 year: 2005 ident: 2022031209251281700_B2 article-title: Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes publication-title: N Engl J Med doi: 10.1056/NEJMoa043980 – volume: 12 start-page: 295 year: 2011 ident: 2022031209251281700_B9 article-title: The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2 publication-title: Nat Immunol doi: 10.1038/ni.2005 – volume: 378 start-page: 319 year: 2011 ident: 2022031209251281700_B28 article-title: Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recent-onset type 1 diabetes: a randomised double-blind trial publication-title: Lancet doi: 10.1016/S0140-6736(11)60895-7 – volume: 210 start-page: 116 year: 2001 ident: 2022031209251281700_B38 article-title: Interleukin-2 activates human peripheral blood eosinophils publication-title: Cell Immunol doi: 10.1006/cimm.2001.1808 – volume: 365 start-page: 2055 year: 2011 ident: 2022031209251281700_B18 article-title: Interleukin-2 and regulatory T cells in graft-versus-host disease publication-title: N Engl J Med doi: 10.1056/NEJMoa1108188 – volume: 365 start-page: 2067 year: 2011 ident: 2022031209251281700_B19 article-title: Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis publication-title: N Engl J Med doi: 10.1056/NEJMoa1105143 – volume: 33 start-page: 301 year: 2010 ident: 2022031209251281700_B10 article-title: The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism publication-title: Immunity doi: 10.1016/j.immuni.2010.09.002 – reference: 22923646 - Diabetes. 2012 Sep;61(9):2214-5
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Snippet	Rapamycin/interleukin-2 (IL-2) combination treatment of NOD mice effectively treats autoimmune diabetes. We performed a phase 1 clinical trial to test the...
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SubjectTerms	Animals Biological and medical sciences Diabetes Mellitus, Type 1 - drug therapy Diabetes Mellitus, Type 1 - immunology Diabetes. Impaired glucose tolerance Dosage and administration Drug therapy Drug Therapy, Combination Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Humans Immunology and Transplantation Insulin-Secreting Cells - drug effects Insulin-Secreting Cells - physiology Interleukin-2 Interleukin-2 - administration & dosage Interleukin-2 - therapeutic use Medical sciences Mice Mice, Inbred NOD Rapamycin Sirolimus Sirolimus - administration & dosage T-Lymphocytes, Regulatory - immunology Type 1 diabetes
Title	Rapamycin/IL-2 Combination Therapy in Patients With Type 1 Diabetes Augments Tregs yet Transiently Impairs β-Cell Function
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