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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...

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Autores principales: Monti, Paolo, Scirpoli, Miriam, Maffi, Paola, Piemonti, Lorenzo, Secchi, Antonio, Bonifacio, Ezio, Roncarolo, Maria-Grazia, Battaglia, Manuela
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
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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.
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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
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