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

175 Citations (Scopus)

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

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Isoantigens
Interleukin-10
T-Lymphocytes
Cytokines
Immune Tolerance
Adoptive Transfer
Graft vs Host Disease
Homeostasis
Transplantation
Maintenance

ASJC Scopus subject areas

  • Immunology

Cite this

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.

Induction of CD4+ T cell alloantigen-specific hyporesponsiveness by IL- 10 and TGF-β. / Zeller, Jay C.; Panoskaltsis-Mortari, Angela; Murphy, William J; Ruscetti, Francis W.; Narula, Satwant; Roncarolo, Maria G.; Blazar, Bruce R.

In: Journal of Immunology, Vol. 163, No. 7, 01.10.1999, p. 3684-3691.

Research output: Contribution to journalArticle

Zeller, JC, Panoskaltsis-Mortari, A, Murphy, WJ, Ruscetti, FW, Narula, S, Roncarolo, MG & Blazar, BR 1999, 'Induction of CD4+ T cell alloantigen-specific hyporesponsiveness by IL- 10 and TGF-β', Journal of Immunology, vol. 163, no. 7, pp. 3684-3691.
Zeller JC, Panoskaltsis-Mortari A, Murphy WJ, Ruscetti FW, Narula S, Roncarolo MG et al. Induction of CD4+ T cell alloantigen-specific hyporesponsiveness by IL- 10 and TGF-β. Journal of Immunology. 1999 Oct 1;163(7):3684-3691.
Zeller, Jay C. ; Panoskaltsis-Mortari, Angela ; Murphy, William J ; Ruscetti, Francis W. ; Narula, Satwant ; Roncarolo, Maria G. ; Blazar, Bruce R. / Induction of CD4+ T cell alloantigen-specific hyporesponsiveness by IL- 10 and TGF-β. In: Journal of Immunology. 1999 ; Vol. 163, No. 7. pp. 3684-3691.
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