B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance

Jang June Park, Ryusuke Omiya, Yumiko Matsumura, Yukimi Sakoda, Atsuo Kuramasu, Mathew M. Augustine, Sheng Yao, Fumihiko Tsushima, Hidehiko Narazaki, Sudarshan Anand, Yingjia Liu, Scott E. Strome, Lieping Chen, Koji Tamada

Research output: Contribution to journalArticle

198 Scopus citations

Abstract

T-cell tolerance is the central program that prevents harmful immune responses against self-antigens, in which inhibitory PD-1 signal given by B7-H1 interaction plays an important role. Recent studies demonstrated that B7-H1 binds CD80 besides PD-1, and B7-H1/CD80 interaction also delivers inhibitory signals in T cells. However, a role of B7-H1/CD80 signals in regulation of T-cell tolerance has yet to be explored. We report here that attenuation of B7-H1/CD80 signals by treatment with anti-B7-H1 monoclonal antibody, which specifically blocks B7-H1/CD80 but not B7-H1/PD-1, enhanced T-cell expansion and prevented T-cell anergy induction. In addition, B7-H1/CD80 blockade restored Ag responsiveness in the previously anergized T cells. Experiments using B7-H1 or CD80-deficient T cells indicated that an inhibitory signal through CD80, but not B7-H1, on T cells is responsible in part for these effects. Consistently, CD80 expression was detected on anergic T cells and further up-regulated when they were reexposed to the antigen (Ag). Finally, blockade of B7-H1/CD80 interaction prevented oral tolerance induction and restored T-cell responsiveness to Ag previously tolerized by oral administration. Taken together, our findings demonstrate that the B7-H1/CD80 pathway is a crucial regulator in the induction and maintenance of T-cell tolerance.

Original languageEnglish (US)
Pages (from-to)1291-1298
Number of pages8
JournalBlood
Volume116
Issue number8
DOIs
StatePublished - Aug 26 2010

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Park, J. J., Omiya, R., Matsumura, Y., Sakoda, Y., Kuramasu, A., Augustine, M. M., Yao, S., Tsushima, F., Narazaki, H., Anand, S., Liu, Y., Strome, S. E., Chen, L., & Tamada, K. (2010). B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance. Blood, 116(8), 1291-1298. https://doi.org/10.1182/blood-2010-01-265975