Rapamycin monotherapy in patients with type 1 diabetes modifies CD4 +CD25+FOXP3+ Regulatory T-Cells

Paolo Monti, Miriam Scirpoli, Paola Maffi, Lorenzo Piemonti, Antonio Secchi, Ezio Bonifacio, Maria Grazia Roncarolo, Manuela Battaglia

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE-Rapamycin is an immunosuppressive drug curently 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.

Original languageEnglish
Pages (from-to)2341-2347
Number of pages7
JournalDiabetes
Volume57
Issue number9
DOIs
Publication statusPublished - Sep 2008

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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