ICOS is essential for effective T-helper-cell responses

Nature. 2001 Jan 4;409(6816):105-9. doi: 10.1038/35051113.


The outcome of T-cell responses after T-cell encounter with specific antigens is modulated by co-stimulatory signals, which are required for both lymphocyte activation and development of adaptive immunity. ICOS, an inducible co-stimulator with homology to CD28, is expressed on activated, but not resting T cells, and shows T-cell co-stimulatory function in vitro. ICOS binds specifically to its counter-receptor B7RP-1 (refs 5,6,7), but not to B7-1 or B7-2. Here we provide in vivo genetic evidence that ICOS delivers a co-stimulatory signal that is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell-dependent antigens. To determine the physiological function of ICOS, we generated and characterized gene-targeted ICOS-deficient mice. In vivo, a lack of ICOS results in severely deficient T-cell-dependent B-cell responses. Germinal centre formation is impaired and immunoglobulin class switching, including production of allergy-mediating IgE, is defective. ICOS-deficient T cells primed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interferon-gamma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / physiology*
  • B-Lymphocytes / immunology
  • Cell Communication
  • Cell Division
  • Cells, Cultured
  • Female
  • Ficoll / analogs & derivatives*
  • Ficoll / immunology
  • Flow Cytometry
  • Gene Targeting
  • Germinal Center / physiology
  • Hemocyanins / immunology
  • Immunoglobulin Class Switching
  • Immunoglobulin G / immunology
  • Inducible T-Cell Co-Stimulator Protein
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / physiology
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / physiology*
  • Trinitrobenzenes / immunology


  • Antigens
  • Antigens, Differentiation, T-Lymphocyte
  • Icos protein, mouse
  • Immunoglobulin G
  • Inducible T-Cell Co-Stimulator Protein
  • TNP-ficoll
  • Trinitrobenzenes
  • Interleukin-4
  • Ficoll
  • Interferon-gamma
  • Hemocyanins
  • keyhole-limpet hemocyanin