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- Title
Rapamycin and Interleukin-10 Treatment Induces T Regulatory Type 1 Cells That Mediate Antigen-Specific Transplantation Tolerance.
- Authors
Battaglia, Manuela; Stabilini, Angela; Draghici, Elena; Gregori, Silvia; Mocchetti, Cristina; Bonifacio, Ezio; Roncarolo, Maria-Grazia
- Abstract
Islet transplantation is a cure for type 1 diabetes, but its potential is limited by the need for constant immunosuppression. One solution to this problem is the induction of transplantation tolerance mediated by T regulatory cells. T regulatory type 1 (Tr1) cells are characterized by their production of high levels of interleukin (IL)-10, which is crucial for their differentiation and suppressive function. We investigated the effects of IL-10 administered in combination with rapamycin on the induction of Tr1 cells that could mediate a state of tolerance in diabetic mice after pancreatic islet transplantation. The efficacy of this treatment was compared with IL-10 alone and standard immunosuppression. Stable long-term tolerance that was not reversible by alloantigen rechallenge was achieved only in mice treated with rapamycin plus IL-10. Tr1 cells that produced high levels of IL-10 and suppressed T-cell proliferation were isolated from splenocytes of rapamycin plus IL-10-treated mice after treatment withdrawal. In rapamycin plus IL-10-treated mice, endogenous IL-10 mediated an active state of tolerance, as was observed when the blockade of IL-10 activity rapidly induced graft rejection > 100 days after transplantation. CD4+ T-cells from rapamycin plus IL-10-treated mice transferred antigen-specific tolerance in mice that received new transplants. Thus rapamycin plus IL-10 not only prevented allograft rejection but also induced Tr1 cells that mediated stable antigen-specific, long-term tolerance in vivo.
- Subjects
TRANSPLANTATION of organs, tissues, etc.; IMMUNOSUPPRESSION; T cells; INTERLEUKIN-10; RAPAMYCIN
- Publication
Diabetes, 2006, Vol 55, Issue 1, p40
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/diabetes.55.01.06.db05-0613