Interferon Regulatory factor-1 Is Required for a T Helper 1 Immune Response in Vivo

Immunity. 1997 Jun;6(6):681-9. doi: 10.1016/s1074-7613(00)80444-6.

Abstract

The transcription factor interferon regulatory factor-1 (IRF-1) mediates the effects of IFN. No information exists on its role in lymphokine production. Protection against the intracellular pathogen Leishmania major depends on a Th1 response. Here, we show that CD4+ T cells from Leishmania-infected mice lacking one (+/-) or both (-/-) alleles of the IRF-1 gene developed a profound, gene dose-dependent decrease in IFNgamma production. IRF-1(-/-) mice showed dramatically exacerbated Leishmaniasis. They produced increased Leishmania-specific IgG1 and IgE, and their CD4+ T cells produced increased IL-4, characteristics of the non-protective Th2 response. In cell transfer experiments, IRF-1(-/-) CD4+ T cells mounted normal Th1 responses. However, the ability of IRF-1(-/-) mice to produce IL-12 was severely compromised. Thus, IRF-1 is a determining factor for Th1 responses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation
  • Cytokines / biosynthesis
  • DNA-Binding Proteins / physiology*
  • Immunity, Cellular
  • Immunity, Innate / immunology
  • Interferon Regulatory Factor-1
  • Interleukin-12 / biosynthesis
  • Leishmania major
  • Leishmaniasis, Cutaneous / immunology
  • Lymph Nodes / cytology
  • Lymphocyte Cooperation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphoproteins / physiology*
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th2 Cells / immunology

Substances

  • Cytokines
  • DNA-Binding Proteins
  • Interferon Regulatory Factor-1
  • Irf1 protein, mouse
  • Phosphoproteins
  • Interleukin-12