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Induction, binding specificity and function of human ICOS.

Recently, we have identified the inducible co-stimulator (ICOS), an activation-dependent, T cell-specific cell surface molecule related to CD28 and CTLA-4. Detailed analysis of human ICOS presented here shows that it is a 55-60-kDa homodimer with differently N-glycosylated subunits of 27 and 29 kDa. ICOS requires both phorbol 12-myristate 13-acetate and ionomycin for full induction, and is sensitive to Cyclosporin A. ICOS is up-regulated early on all T cells, including the CD28- subset, and continues to be expressed into later phases of T cell activation. On stimulation of T cells by antigen-presenting cells, the CD28/B7, but not the CD40 ligand/CD40 pathway is critically involved in the induction of ICOS. ICOS does not bind to B7-1 or B7-2, and CD28 does not bind to ICOS ligand; thus the CD28 and ICOS pathways do not cross-interact on the cell surface. In vivo, ICOS is expressed in the medulla of the fetal and newborn thymus, in the T cell zones of tonsils and lymph nodes, and in the apical light zones of germinal centers (predominant expression). Functionally, ICOS co-induces a variety of cytokines including IL-4, IL-5, IL-6, IFN-gamma, TNF-alpha, GM-CSF, but not IL-2, and superinduces IL-10. Furthermore, ICOS co-stimulation prevents the apoptosis of pre-activated T cells. The human ICOS gene maps to chromosome 2q33 - 34.

Pubmed ID: 11169414

Authors

  • Beier KC
  • Hutloff A
  • Dittrich AM
  • Heuck C
  • Rauch A
  • B├╝chner K
  • Ludewig B
  • Ochs HD
  • Mages HW
  • Kroczek RA

Journal

European journal of immunology

Publication Data

December 25, 2000

Associated Grants

None

Mesh Terms

  • Antigens, CD28
  • Antigens, CD40
  • Antigens, CD80
  • Antigens, Differentiation, T-Lymphocyte
  • Apoptosis
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Chromosome Mapping
  • Cyclosporine
  • Cytokines
  • Dimerization
  • Glycosylation
  • Humans
  • Inducible T-Cell Co-Stimulator Protein