Item Type: | Article |
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Title: | ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28 |
Creators Name: | Hutloff, A., Dittrich, A.M., Beier, K.C., Eljaschewitsch, B., Kraft, R., Anagnostopoulos, I. and Kroczek, R.A. |
Abstract: | The T-cell-specific cell-surface receptors CD28 and CTLA-4 are important regulators of the immune system. CD28 potently enhances those T-cell functions that are essential for an effective antigen-specific immune response, and the homologous CTLA-4 counterbalances the CD28-mediated signals and thus prevents an otherwise fatal overstimulation of the lymphoid system. Here we report the identification of a third member of this family of molecules, inducible co-stimulator (ICOS), which is a homodimeric protein of relative molecular mass 55,000-60,000 (M(r) 55K-60K). Matching CD28 in potency, ICOS enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, upregulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B cells. Unlike the constitutively expressed CD28, ICOS has to be de novo induced on the T-cell surface, does not upregulate the production of interleukin-2, but superinduces the synthesis of interleukin-10, a B-cell-differentiation factor. In vivo, ICOS is highly expressed on tonsillar T cells, which are closely associated with B cells in the apical light zone of germinal centres, the site of terminal B-cell maturation. Our results indicate that ICOS is another major regulator of the adaptive immune system. |
Keywords: | Amino Acid Sequence, CD28 Antigens, Cell Communication, Cell Line, Germinal Center, Inducible T-Cell Co-Stimulator Protein, Lymphocyte Activation, Molecular Cloning, Molecular Sequence Data, Monoclonal Antibodies, T-Lymphocyte Differentiation Antigens, T-Lymphocytes, Animals, Mice |
Source: | Nature |
ISSN: | 0028-0836 |
Publisher: | Nature Publishing Group |
Volume: | 397 |
Number: | 6716 |
Page Range: | 263-266 |
Date: | 21 January 1999 |
Official Publication: | https://doi.org/10.1038/16717 |
PubMed: | View item in PubMed |
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