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Induction of CD4(+) T cell alloantigen-specific hyporesponsiveness by IL-10 and TGF-beta(1)
Induction of CD4(+) T cell alloantigen-specific hyporesponsiveness by IL-10 and TGF-beta(1) JOURNAL OF IMMUNOLOGY Zeller, J. C., Panoskaltsis-Mortari, A., Murphy, W. J., Ruscetti, F. W., Narula, S., Roncarolo, M. G., Blazar, B. R. 1999; 163 (7): 3684-3691Abstract
Induction and maintenance of Ag-specific tolerance are pivotal for immune homeostasis, prevention of autoimmune disorders, and the goal of transplantation. Recent studies suggest that certain cytokines, notably IL-10 and TGF-beta, may play a role in down-regulating immune functions. To further examine the role of cytokines in Ag-specific hyporesponsiveness, murine CD4+ T cells were exposed ex vivo to alloantigen-bearing stimulators in the presence of exogenous IL-10 and/or TGF-beta. Primary but not secondary alloantigen proliferative responses were inhibited by IL-10 alone. However, the combined addition of IL-10 + TGF-beta markedly induced alloantigen hyporesponsiveness in both primary and secondary MLR cultures. Alloantigen-specific hyporesponsiveness was observed also under conditions in which nominal Ag responses were intact. In adoptive transfer experiments, IL-10 + TGF-beta-treated CD4+ T cells, but not T cells treated with either cytokine alone, were markedly impaired in inducing graft-vs-host disease alloresponses to MHC class II disparate recipients. These data provide the first formal evidence that IL-10 and TGF-beta have at least an additive effect in inducing alloantigen-specific tolerance, and that in vitro cytokines can be exploited to suppress CD4+ T cell-mediated Ag-specific responses in vivo.
View details for Web of Science ID 000082744900017
View details for PubMedID 10490963