Regulation of IFN-γ signaling is essential for the cytotoxic activity of CD8+ T cells

G. Z. Tau, S. N. Cowan, J. Weisburg, N. S. Braunstein, P. B. Rothman

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies have demonstrated that, as naive murine CD4+ cells differentiate into Th1 cells, they lose expression of the second chain of IFN-γR (IFN-γR2). Hence, the IFN-γ-producing subset of Th cells is unresponsive to IFN-γ. Analysis of IFN-γ-producing CD8+ T cells demonstrates that, like Th1 cells, these cells do not express IFN-γR2. To define the importance of IFN-γ signaling for the development of functional CD8+ T cells, mice either lacking IFN-γR2 or overexpressing this protein were examined. While CD8+ T cell development and function appear normal in IFN-γR2-/- mice, CD8+ T cell function in IFN-γR2 transgenic is altered. IFN-γR2 transgenic CD8+ T cells are unable to lyse target cells in vitro. However, these cells produce Fas ligand, perforin, and granzyme B, the effector molecules required for killing. Interestingly, TG CD8+ T cells proliferate normally and produce cytokines, such as IFN-γ in response to antigenic stimulation. Therefore, although IFN-γ signaling is not required for the generation of normal cytotoxic T cells, constitutive IFN-γ signaling can selectively impair the cytotoxic function of CD8+ T cells.

Original languageEnglish (US)
Pages (from-to)5574-5582
Number of pages9
JournalJournal of Immunology
Volume167
Issue number10
DOIs
StatePublished - Nov 15 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Regulation of IFN-γ signaling is essential for the cytotoxic activity of CD8<sup>+</sup> T cells'. Together they form a unique fingerprint.

Cite this