Development of Th1-type Immune Responses Requires the Type I Cytokine Receptor TCCR

Nature. 2000 Oct 19;407(6806):916-20. doi: 10.1038/35038103.

Abstract

On antigen challenge, T-helper cells differentiate into two functionally distinct subsets, Th1 and Th2, characterized by the different effector cytokines that they secrete. Th1 cells produce interleukin (IL)-2, interferon-gamma (IFN-gamma) and lymphotoxin-beta, which mediate pro-inflammatory functions critical for the development of cell-mediated immune responses, whereas Th2 cells secrete cytokines such as IL-4, IL-5 and IL-10 that enhance humoral immunity. This process of T-helper cell differentiation is tightly regulated by cytokines. Here we report a new member of the type I cytokine receptor family, designated T-cell cytokine receptor (TCCR). When challenged in vivo with protein antigen, TCCR-deficient mice had impaired Th1 response as measured by IFN-gamma production. TCCR-deficient mice also had increased susceptibility to infection with an intracellular pathogen, Listeria monocytogenes. In addition, levels of antigen-specific immunoglobulin-gamma2a, which are dependent on Th1 cells, were markedly reduced in these mice. Our results demonstrate the existence of a new cytokine receptor involved in regulating the adaptive immune response and critical to the generation of a Th1 response.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Female
  • Gene Targeting
  • Hemocyanins / immunology
  • Humans
  • Immunoglobulin Isotypes / immunology
  • Interferon-gamma / biosynthesis
  • Leukopoiesis / physiology
  • Listeria monocytogenes / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / immunology
  • Receptors, Cytokine / isolation & purification*
  • Receptors, Cytokine / metabolism
  • Sequence Homology, Amino Acid
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Tissue Distribution

Substances

  • Il27ra protein, mouse
  • Immunoglobulin Isotypes
  • Receptors, Cytokine
  • Interferon-gamma
  • Hemocyanins
  • keyhole-limpet hemocyanin

Associated data

  • GENBANK/AF265242
  • GENBANK/AF265243