Cutting edge: early IL-4 production governs the requirement for IL-27-WSX-1 signaling in the development of protective Th1 cytokine responses following Leishmania major infection

J Immunol. 2004 Apr 15;172(8):4672-5. doi: 10.4049/jimmunol.172.8.4672.

Abstract

There are conflicting reports on the requirements for the IL-27-WSX-1 pathway in the development of Th type 1 responses and resistance to intracellular pathogens; although early IFN-gamma production and resistance to Leishmania major are impaired in the absence of WSX-1 signaling, WSX-1(-/-) mice generate robust IFN-gamma responses and control infection with other intracellular protozoan pathogens. In this report, we resolve these conflicting observations and demonstrate that, in the absence of IL-4, WSX-1 is not required for early IFN-gamma production and control of L. major. Thus, the requirement for WSX-1 signaling in Th type 1 cell differentiation is restricted to conditions in which IL-4 is produced.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / pharmacology
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / biosynthesis
  • Interleukin-4 / antagonists & inhibitors
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / immunology
  • Interleukin-4 / physiology
  • Interleukins / physiology*
  • Interphase / genetics
  • Interphase / immunology
  • Leishmania major / growth & development
  • Leishmania major / immunology*
  • Leishmaniasis, Cutaneous / immunology*
  • Leishmaniasis, Cutaneous / parasitology
  • Leishmaniasis, Cutaneous / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Cytokine / deficiency
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / physiology*
  • Receptors, Interleukin
  • Signal Transduction / immunology*
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th1 Cells / parasitology
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Cytokines
  • Il27 protein, mouse
  • Il27ra protein, mouse
  • Interleukins
  • Receptors, Cytokine
  • Receptors, Interleukin
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma