Failure to suppress the expansion of the activated CD4 T cell population in interferon γ-deficient mice leads to exacerbation of experimental autoimnaune encephalomyelitis

Cong-Qiu Chu, Susan Wittmer, Dyana K. Dalton

Research output: Contribution to journalArticle

349 Citations (Scopus)

Abstract

Mice deficient in interferon (IFN)-γ or IFN-γ receptor develop progressive and fatal experimental autoimmune encephalomyelitis (EAE). We demonstrate that CD4 T cells lacking IFN-γ production were required to passively transfer EAE, indicating that they were disease-mediating cells in IFN-γ knockout (KO) mice. IFN-γ KO mice accumulated 10-16-fold more activated CD4 T cells (CD4+CD44(hi)) than wild-type mice in the central nervous system during EAE. CD4+CD44(hi) T cells in the spleen and central nervous system of IFN-γ KO mice during EAE showed markedly increased in vivo proliferation and significantly decreased ex vivo apoptosis compared with those of wild-type mice. IFN-ψ KO CD4+CD44(hi) T cells proliferated extensively to antigen restimulation in vitro and accumulated larger numbers of live CD4+ CD44(hi) T cells. IFN-γ completely suppressed proliferation and significantly induced apoptosis of CD4+CD44(hi) T cells responding to antigen and hence inhibited accumulation of live, activated CD4 T cells. We thus present novel in vivo and in vitro evidence that IFN-> may limit the extent of EAE by suppressing expansion of activated CD4 T cells.

Original languageEnglish (US)
Pages (from-to)123-128
Number of pages6
JournalJournal of Experimental Medicine
Volume192
Issue number1
DOIs
StatePublished - Jul 3 2000
Externally publishedYes

Fingerprint

Encephalomyelitis
Interferons
Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Population
Knockout Mice
Central Nervous System
Interferon Receptors
Apoptosis
Antigens
Spleen

Keywords

  • Animal disease models
  • Apoptosis
  • Autoimmune diseases
  • Knockout mice
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Failure to suppress the expansion of the activated CD4 T cell population in interferon γ-deficient mice leads to exacerbation of experimental autoimnaune encephalomyelitis. / Chu, Cong-Qiu; Wittmer, Susan; Dalton, Dyana K.

In: Journal of Experimental Medicine, Vol. 192, No. 1, 03.07.2000, p. 123-128.

Research output: Contribution to journalArticle

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