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ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28

Nature volume 397, pages 263–266 (1999)Cite this article

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 response1,2,3,4,5, and the homologous CTLA-4 counterbalances the CD28-mediated signals and thus prevents an otherwise fatal overstimulation of the lymphoid system6,7,8,9. 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 (Mr 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.

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Figure 1: Identification, purification and cloning of ICOS.
Figure 2: Co-stimulatory functions of ICOS.
Figure 3: Expression of ICOS on tonsillar T cells.

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Acknowledgements

We thank J. Ledbetter for the gift of monoclonal antibody 9.3; J. Slupsky for critical reading of the manuscript; and K. Ranke for technical assistance.

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Author notes

  1. Anna M. Dittrich, Katja C. Beier and Ionnis Anagnostopoulos: These authors contributed equally to this work

Authors and Affiliations

  1. Molecular Immunology, Robert Koch-Institut, Nordufer, 13353 20, Berlin, Germany

    Andreas Hutloff, Anna M. Dittrich, Katja C. Beier, Barbara Eljaschewitsch & Richard A. Kroczek

  2. Department of Protein Chemistry, Max-Delbrck-Centrum, Robert-Rssle-Str. 10, 13122, Berlin, Germany

    Regine Kraft

  3. Institute of Pathology, Klinikum Benjamin Franklin, Freie Universitt Berlin, Hindenburgdamm, 12200 30, Berlin, Germany

    Ionnis Anagnostopoulos

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Correspondence to Richard A. Kroczek.

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Hutloff, A., Dittrich, A., Beier, K. et al. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature 397, 263–266 (1999). https://doi.org/10.1038/16717

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