Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion

Abstract

The B7 family members B7-1 and B7-2 interact with CD28 and constitute an essential T-cell co-stimulatory pathway in the initiation of antigen-specific humoral and cell-mediated immune response. Here, we describe a third member of the B7 family, called B7-H1 that does not bind CD28, cytotoxic T-lymphocyte A4 or ICOS (inducible co-stimulator). Ligation of B7-H1 co-stimulated T-cell responses to polyclonal stimuli and allogeneic antigens, and preferentially stimulated the production of interleukin-10. Interleukin-2, although produced in small amounts, was required for the effect of B7-H1 co-stimulation. Our studies thus define a previously unknown co-stimulatory molecule that may be involved in the negative regulation of cell-mediated immune responses.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Characterization and expression pattern of human B7-H1.
Figure 2: Binding of B7-H1 to CTLA4, ICOS and CD28.
Figure 3: Co-stimulation of T-cell growth by B7-H1Ig.
Figure 4: Cytokine secretion of resting T cells by B7-H1 co-stimulation.
Figure 5: B7-H1-co-stimulated T-cell proliferation and IL-10 production is IL-2-dependent.

Similar content being viewed by others

References

  1. Chambers, C.A. & Allison, J.P. Co-stimulation in T cell responses. Curr. Opin. Immunol. 9, 369– 404 (1997).

    Article  Google Scholar 

  2. Lenschow, D.J., Walunas, T.L. & Bluestone, J.A. CD28/B7 system of T cell costimulation. Annu. Rev. Immunol. 14, 233–258 (1996).

    Article  CAS  Google Scholar 

  3. Chen, L., Linsley, P.S. & Hellstrom, K.E. Costimulation of T cells for tumor immunity. Immunol. Today 14, 483–486 (1993).

    Article  CAS  Google Scholar 

  4. Boise, L.H., Noel, P.J. & Thompson, C.B. CD28 and apoptosis. Curr. Opin. Immunol. 7, 620–625 (1995).

    Article  CAS  Google Scholar 

  5. Krummel, M.F. & Allison, J.P. CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells. J. Exp. Med. 183, 2533– 2540 (1996).

    Article  CAS  Google Scholar 

  6. Walunas, T.L., Bakker, C.Y. & Bluestone, J.A. CTLA-4 ligation blocks CD28-dependent T cell activation. J. Exp. Med. 183, 2541– 2550 (1996).

    Article  CAS  Google Scholar 

  7. Hutloff, A. et al. ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature 397, 263–266 (1999).

    Article  CAS  Google Scholar 

  8. Moore, K.W. et al. Interleukin-10. Annu. Rev. Immunol. 11, 165–190 (1993).

    Article  CAS  Google Scholar 

  9. Freeman, G.J. et al. Cloning of B7-2: a CTLA-4 counter-receptor that costimulates human T cell proliferation. Science 262, 909–911 (1993).

    Article  CAS  Google Scholar 

  10. Azuma, M. et al. B70 antigen is a second ligand for CTLA-4 and CD28. Nature 366, 76–79 (1993).

    Article  CAS  Google Scholar 

  11. Peach, R.J. et al. Both extracellular immunoglobulin-like domains of CD80 contain residues critical for binding T cell surface receptor CTLA-4 and CD28. J. Biol. Chem. 270, 21181–21187 (1995).

    Article  CAS  Google Scholar 

  12. Fargeas, C.A. et al. Identification of residues in the V domain of CD80 (B7-1) implicated in functional interactions with CD28 and CTLA-4. J. Exp. Med. 182, 667–675 (1995).

    Article  CAS  Google Scholar 

  13. Bajorath, J., Peach, R. J. & Linsley, P. S. Immunoglobulin fold characteristics of B7-1 (CD80) and B7-2 (CD86). Protein Sci. 3, 2148– 2150 (1994).

    Article  CAS  Google Scholar 

  14. Linsley, P.S. et al. Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity 1, 793–801 (1994).

    Article  CAS  Google Scholar 

  15. Inaba, K. et al. The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro . J. Exp. Med. 180, 1849– 1860 (1994).

    Article  CAS  Google Scholar 

  16. Freeman, G. J. et al. B7-1 and B7-2 do not deliver identical costimulatory signals since B7-2 but not B7-1 preferentially costimulates the initial production of IL-4. Immunity 2, 523– 532 (1995).

    Article  CAS  Google Scholar 

  17. Nakajima, A. et al. Requirement of CD28-CD86 co-stimulation in the interaction between antigen-primed T helper type 2 and B cells. Int. Immunol. 9, 637–644 (1997).

    Article  CAS  Google Scholar 

  18. Schwartz, R. H. T cell clonal anergy. Curr. Opin. Immunol. 9, 351–357 (1997).

    Article  CAS  Google Scholar 

  19. Georgescu, L, Vakkalanka, R.K, Elkon, K.B. & Crow, M.K. Interleukin-10 promotes activation-induced cell death of SLE lymphocytes mediated by Fas ligand. J. Clin. Invest. 100, 2622 –2633 (1997).

    Article  CAS  Google Scholar 

  20. Goerdt, S. & Orfanos, C. E. Other functions, other genes: Alternative activation of antigen-presenting cells. Immunity 10, 137–142 (1999).

    Article  CAS  Google Scholar 

  21. Li, Y., McGowan, P., Hellstrom, K.E. & Chen, L. Costimulation of tumor-reactive CD4+ and CD8+ T lymphocytes by B7, a natural ligand for CD28, can be used to treat established mouse melanoma. J. Immunol. 153, 421–428 (1994).

    CAS  PubMed  Google Scholar 

  22. Chen, L. et al. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 71, 1093–1102 (1992).

    Article  CAS  Google Scholar 

  23. Li, Y., Hellstrom, K.E., Newby, S.A. & Chen, L. Costimulation by CD48 and B7-1 induces immunity against poorly immunogenic tumors. J. Exp. Med. 183, 639–644 (1996).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank J. Lau and K. Jensen for editing the manuscript. This work was supported in part by the Mayo Foundation and National Institutes of Health grant CA79915. G.Z. is supported by National Institutes of Health training grant CA09127. The accession number for the human B7-H1 sequence in the GenBank is AF177937.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lieping Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dong, H., Zhu, G., Tamada, K. et al. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med 5, 1365–1369 (1999). https://doi.org/10.1038/70932

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/70932

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing