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ICOS co-stimulatory receptor is essential for T-cell activation and function

Author

Listed:
  • Chen Dong

    (Howard Hughes Medical Institute, Section of Immunobiology
    Yale University School of Medicine
    University of Washington School of Medicine)

  • Amy E. Juedes

    (Yale University School of Medicine)

  • Ulla-Angela Temann

    (Howard Hughes Medical Institute, Section of Immunobiology
    Yale University School of Medicine)

  • Sujan Shresta

    (University of California at Berkeley)

  • James P. Allison

    (University of California at Berkeley)

  • Nancy H. Ruddle

    (Yale University School of Medicine)

  • Richard A. Flavell

    (Howard Hughes Medical Institute, Section of Immunobiology
    Yale University School of Medicine)

Abstract

T-lymphocyte activation and immune function are regulated by co-stimulatory molecules. CD28, a receptor for B7 gene products, has a chief role in initiating T-cell immune responses1,2. CTLA4, which binds B7 with a higher affinity, is induced after T-cell activation and is involved in downregulating T-cell responses3,4. The inducible co-stimulatory molecule (ICOS), a third member of the CD28/CTLA4 family, is expressed on activated T cells5,6. Its ligand B7H/B7RP-1 is expressed on B cells and in non-immune tissues after injection of lipopolysaccharide into animals6,7. To understand the role of ICOS in T-cell activation and function, we generated and analysed ICOS-deficient mice. Here we show that T-cell activation and proliferation are defective in the absence of ICOS. In addition, ICOS-/- T cells fail to produce interleukin-4 when differentiated in vitro or when primed in vivo. ICOS is required for humoral immune responses after immunization with several antigens. ICOS-/- mice showed greatly enhanced susceptibility to experimental autoimmune encephalomyelitis, indicating that ICOS has a protective role in inflammatory autoimmune diseases.

Suggested Citation

  • Chen Dong & Amy E. Juedes & Ulla-Angela Temann & Sujan Shresta & James P. Allison & Nancy H. Ruddle & Richard A. Flavell, 2001. "ICOS co-stimulatory receptor is essential for T-cell activation and function," Nature, Nature, vol. 409(6816), pages 97-101, January.
    • Handle: RePEc:nat:nature:v:409:y:2001:i:6816:d:10.1038_35051100
    DOI: 10.1038/35051100
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    Cited by:

    1. Carleigh A O’Brien & Tajie H Harris, 2020. "ICOS-deficient and ICOS YF mutant mice fail to control Toxoplasma gondii infection of the brain," PLOS ONE, Public Library of Science, vol. 15(1), pages 1-16, January.

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