Induction of CD4+ T cell alloantigen-specific hyporesponsiveness by IL- 10 and TGF-β

Jay C. Zeller, Angela Panoskaltsis-Mortari, William J Murphy, Francis W. Ruscetti, Satwant Narula, Maria G. Roncarolo, Bruce R. Blazar

Research output: Contribution to journalArticle

176 Scopus citations

Abstract

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-β, 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-β. Primary but not secondary alloantigen proliferative responses were inhibited by IL-10 alone. However, the combined addition of IL-10 + TGF-β 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-β-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 H disparate recipients. These data provide the first formal evidence that IL-10 and TGF-β 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.

Original languageEnglish (US)
Pages (from-to)3684-3691
Number of pages8
JournalJournal of Immunology
Volume163
Issue number7
StatePublished - Oct 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Zeller, J. C., Panoskaltsis-Mortari, A., Murphy, W. J., Ruscetti, F. W., Narula, S., Roncarolo, M. G., & Blazar, B. R. (1999). Induction of CD4+ T cell alloantigen-specific hyporesponsiveness by IL- 10 and TGF-β. Journal of Immunology, 163(7), 3684-3691.