Cargando…
Rapamycin Monotherapy in Patients With Type 1 Diabetes Modifies CD4(+)CD25(+)FOXP3(+) Regulatory T-Cells
OBJECTIVE—Rapamycin is an immunosuppressive drug currently used to prevent graft rejection in humans, which is considered permissive for tolerance induction. Rapamycin allows expansion of both murine and human naturally occurring CD4(+)CD25(+)FOXP3(+) T regulatory cells (nTregs), which are pivotal f...
Autores principales: | , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2008
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518485/ https://www.ncbi.nlm.nih.gov/pubmed/18559659 http://dx.doi.org/10.2337/db08-0138 |
_version_ | 1782158575326461952 |
---|---|
author | Monti, Paolo Scirpoli, Miriam Maffi, Paola Piemonti, Lorenzo Secchi, Antonio Bonifacio, Ezio Roncarolo, Maria-Grazia Battaglia, Manuela |
author_facet | Monti, Paolo Scirpoli, Miriam Maffi, Paola Piemonti, Lorenzo Secchi, Antonio Bonifacio, Ezio Roncarolo, Maria-Grazia Battaglia, Manuela |
author_sort | Monti, Paolo |
collection | PubMed |
description | OBJECTIVE—Rapamycin is an immunosuppressive drug currently used to prevent graft rejection in humans, which is considered permissive for tolerance induction. Rapamycin allows expansion of both murine and human naturally occurring CD4(+)CD25(+)FOXP3(+) T regulatory cells (nTregs), which are pivotal for the induction and maintenance of peripheral tolerance. Preclinical murine models have shown that rapamycin enhances nTreg proliferation and regulatory function also in vivo. Objective of this study was to assess whether rapamycin has in vivo effects on human nTregs. RESEARCH DESIGN AND METHODS—nTreg numbers and function were examined in a unique set of patients with type 1 diabetes who underwent rapamycin monotherapy before islet transplantation. RESULTS—We found that rapamycin monotherapy did not alter the frequency and functional features, namely proliferation and cytokine production, of circulating nTregs. However, nTregs isolated from type 1 diabetic patients under rapamycin treatment had an increased capability to suppress proliferation of CD4(+)CD25(−) effector T-cells compared with that before treatment. CONCLUSIONS—These findings demonstrate that rapamycin directly affects human nTreg function in vivo, which consists of refitting their suppressive activity, whereas it does not directly change effector T-cell function. |
format | Text |
id | pubmed-2518485 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-25184852009-09-01 Rapamycin Monotherapy in Patients With Type 1 Diabetes Modifies CD4(+)CD25(+)FOXP3(+) Regulatory T-Cells Monti, Paolo Scirpoli, Miriam Maffi, Paola Piemonti, Lorenzo Secchi, Antonio Bonifacio, Ezio Roncarolo, Maria-Grazia Battaglia, Manuela Diabetes Immunology and Transplantation OBJECTIVE—Rapamycin is an immunosuppressive drug currently used to prevent graft rejection in humans, which is considered permissive for tolerance induction. Rapamycin allows expansion of both murine and human naturally occurring CD4(+)CD25(+)FOXP3(+) T regulatory cells (nTregs), which are pivotal for the induction and maintenance of peripheral tolerance. Preclinical murine models have shown that rapamycin enhances nTreg proliferation and regulatory function also in vivo. Objective of this study was to assess whether rapamycin has in vivo effects on human nTregs. RESEARCH DESIGN AND METHODS—nTreg numbers and function were examined in a unique set of patients with type 1 diabetes who underwent rapamycin monotherapy before islet transplantation. RESULTS—We found that rapamycin monotherapy did not alter the frequency and functional features, namely proliferation and cytokine production, of circulating nTregs. However, nTregs isolated from type 1 diabetic patients under rapamycin treatment had an increased capability to suppress proliferation of CD4(+)CD25(−) effector T-cells compared with that before treatment. CONCLUSIONS—These findings demonstrate that rapamycin directly affects human nTreg function in vivo, which consists of refitting their suppressive activity, whereas it does not directly change effector T-cell function. American Diabetes Association 2008-09 /pmc/articles/PMC2518485/ /pubmed/18559659 http://dx.doi.org/10.2337/db08-0138 Text en Copyright © 2008, American Diabetes Association https://creativecommons.org/licenses/by-nc-nd/3.0/Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Immunology and Transplantation Monti, Paolo Scirpoli, Miriam Maffi, Paola Piemonti, Lorenzo Secchi, Antonio Bonifacio, Ezio Roncarolo, Maria-Grazia Battaglia, Manuela Rapamycin Monotherapy in Patients With Type 1 Diabetes Modifies CD4(+)CD25(+)FOXP3(+) Regulatory T-Cells |
title | Rapamycin Monotherapy in Patients With Type 1 Diabetes Modifies CD4(+)CD25(+)FOXP3(+) Regulatory T-Cells |
title_full | Rapamycin Monotherapy in Patients With Type 1 Diabetes Modifies CD4(+)CD25(+)FOXP3(+) Regulatory T-Cells |
title_fullStr | Rapamycin Monotherapy in Patients With Type 1 Diabetes Modifies CD4(+)CD25(+)FOXP3(+) Regulatory T-Cells |
title_full_unstemmed | Rapamycin Monotherapy in Patients With Type 1 Diabetes Modifies CD4(+)CD25(+)FOXP3(+) Regulatory T-Cells |
title_short | Rapamycin Monotherapy in Patients With Type 1 Diabetes Modifies CD4(+)CD25(+)FOXP3(+) Regulatory T-Cells |
title_sort | rapamycin monotherapy in patients with type 1 diabetes modifies cd4(+)cd25(+)foxp3(+) regulatory t-cells |
topic | Immunology and Transplantation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518485/ https://www.ncbi.nlm.nih.gov/pubmed/18559659 http://dx.doi.org/10.2337/db08-0138 |
work_keys_str_mv | AT montipaolo rapamycinmonotherapyinpatientswithtype1diabetesmodifiescd4cd25foxp3regulatorytcells AT scirpolimiriam rapamycinmonotherapyinpatientswithtype1diabetesmodifiescd4cd25foxp3regulatorytcells AT maffipaola rapamycinmonotherapyinpatientswithtype1diabetesmodifiescd4cd25foxp3regulatorytcells AT piemontilorenzo rapamycinmonotherapyinpatientswithtype1diabetesmodifiescd4cd25foxp3regulatorytcells AT secchiantonio rapamycinmonotherapyinpatientswithtype1diabetesmodifiescd4cd25foxp3regulatorytcells AT bonifacioezio rapamycinmonotherapyinpatientswithtype1diabetesmodifiescd4cd25foxp3regulatorytcells AT roncarolomariagrazia rapamycinmonotherapyinpatientswithtype1diabetesmodifiescd4cd25foxp3regulatorytcells AT battagliamanuela rapamycinmonotherapyinpatientswithtype1diabetesmodifiescd4cd25foxp3regulatorytcells |