Induction, binding specificity and function of human ICOS

Eur J Immunol. 2000 Dec;30(12):3707-17. doi: 10.1002/1521-4141(200012)30:12<3707::AID-IMMU3707>3.0.CO;2-Q.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / physiology*
  • Apoptosis
  • B7-1 Antigen / physiology
  • CD28 Antigens / physiology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD40 Antigens / physiology
  • CD8-Positive T-Lymphocytes / metabolism
  • Chromosome Mapping
  • Cyclosporine / pharmacology
  • Cytokines / biosynthesis
  • Dimerization
  • Glycosylation
  • Humans
  • Inducible T-Cell Co-Stimulator Protein


  • Antigens, Differentiation, T-Lymphocyte
  • B7-1 Antigen
  • CD28 Antigens
  • CD40 Antigens
  • Cytokines
  • ICOS protein, human
  • Inducible T-Cell Co-Stimulator Protein
  • Cyclosporine