Low dose TGF-β attenuates IL-12 responsiveness in murine Th cells

James D. Gorham, Mehmet L. Güler, Domenic Fenoglio, Ueli Gubler, Kenneth M. Murphy

Research output: Contribution to journalArticle

95 Scopus citations

Abstract

Expression of IL-12Rs is one important checkpoint for Th1 development. BALB/c DO11.10 CD4+ T cells stimulated by Ag in neutral conditions lose expression of the IL-12R β2 subunit and become unresponsive to IL-12. In contrast, B10.D2 or F1 (BALB/c x B10.D2) DO11.10 CD4+ T cells maintain IL- 12Rβ2 expression when stimulated similarly. Here we show that the loss of IL-12 responsiveness by BALB/c T cells involves the action of endogenous TGF- β. BALB/c T cells stimulated in the presence of anti-TGF-β specifically maintain IL-12 responsiveness, express IL-12Rβ2 mRNA, and can stimulate nitric oxide production in peritoneal exudate cells. Low concentrations of TGF-β added exogenously during primary activation of B10.D2 or F1 T cells significantly inhibit their development of IL-12 responsiveness. These effects of anti-TGF-β are dependent on endogenous IFN-γ and are inhibited by exogenously added IL-4. Thus, at least one effect of TGF-β on Th1/Th2 development may be the attenuation of IL-12Rβ2 expression.

Original languageEnglish
Pages (from-to)1664-1670
Number of pages7
JournalJournal of Immunology
Volume161
Issue number4
StatePublished - Aug 15 1998

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    Gorham, J. D., Güler, M. L., Fenoglio, D., Gubler, U., & Murphy, K. M. (1998). Low dose TGF-β attenuates IL-12 responsiveness in murine Th cells. Journal of Immunology, 161(4), 1664-1670.