Interferon γ signaling alters the function of T helper type 1 cells

Gregory Z. Tau, Thierry Von Der Weid, Binfeng Lu, Simone Cowan, Marina Kvatyuk, Alessandra Pernis, Giorgio Cattoretti, Ned S. Braunstein, Robert L. Coffman, Paul B. Rothman

Research output: Contribution to journalArticlepeer-review

Abstract

One mechanism regulating the ability of different subsets of T helper (Th) cells to respond to cytokines is the differential expression of cytokine receptors. For example, Th2 cells express both chains of the interferon γ receptor (IFN-γR), whereas Th1 cells do not express the second chain of the IFN-γR (IFN-γR2) and are therefore unresponsive to IFN-γ. To determine whether the regulation of IFN-γR2 expression, and therefore IFN-γ responsiveness, is important for the differentiation of naive CD4+ T cells into Th1 cells or for Th1 effector function, we generated mice in which transgenic (TG) expression of IFN-γR2 is controlled by the CD2 promoter and enhancer. CD4+ T cells from IFN-γR2 TG mice exhibit impaired Th1 polarization potential in vitro. TG mice also display several defects in Th1-dependent immunity in vivo, including attenuated delayed-type hypersensitivity responses and decreased antigen-specific IFN-γ production. In addition, TG mice mount impaired Th1 responses against Leishmania major, as manifested by increased parasitemia and more severe lesions than their wild-type littermates. Together, these data suggest that the sustained expression of IFN-γR2 inhibits Th1 differentiation and function. Therefore, the acquisition of an IFN-γ-unresponsive phenotype in Th1 cells plays a crucial role in the development and function of these cells.

Original languageEnglish (US)
Pages (from-to)977-986
Number of pages10
JournalJournal of Experimental Medicine
Volume192
Issue number7
DOIs
StatePublished - Oct 2 2000
Externally publishedYes

Keywords

  • Cytokines
  • Hypersensitivity, delayed
  • Interferon receptors
  • Interferon type II
  • T helper type 1 cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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