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

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 responses. CTLA4, which binds B7 with a higher affinity, is induced after T-cell activation and is involved in downregulating T-cell responses. The inducible co-stimulatory molecule (ICOS), a third member of the CD28/CTLA4 family, is expressed on activated T cells. Its ligand B7H/B7RP-1 is expressed on B cells and in non-immune tissues after injection of lipopolysaccharide into animals. 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.

Pubmed ID: 11343121


  • Dong C
  • Juedes AE
  • Temann UA
  • Shresta S
  • Allison JP
  • Ruddle NH
  • Flavell RA



Publication Data

January 4, 2001

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Antibody Formation
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Cell Differentiation
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental
  • Gene Targeting
  • Hemocyanin
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukin-13
  • Interleukin-4
  • Lymph Nodes
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • T-Lymphocytes