ICOS is essential for effective T-helper-cell responses Academic Article uri icon

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abstract

  • 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.

authors

  • Tafuri, Anna
  • Shahinian, Arda
  • Bladt, Friedhelm
  • Yoshinaga, Steve K
  • Jordana, Manel
  • Wakeham, Andrew
  • Boucher, Louis-Martin
  • Bouchard, Denis
  • Chan, Vera SF
  • Duncan, Gordon
  • Odermatt, Bernhard
  • Ho, Alexandra
  • Itie, Annick
  • Horan, Tom
  • Whoriskey, John S
  • Pawson, Tony
  • Penninger, Josef M
  • Ohashi, Pamela S
  • Mak, Tak W

publication date

  • January 2001

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