B7-H5 costimulates human T cells via CD28H

Yuwen Zhu, Sheng Yao, Bettina P. Iliopoulou, Xue Han, Mathew M. Augustine, Haiying Xu, Ryan T. Phennicie, Sarah J. Flies, Megan Broadwater, William Ruff, Janis M. Taube, Linghua Zheng, Liqun Luo, Gefeng Zhu, Jianzhu Chen, Lieping Chen

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

The B7/CD28 family has profound modulatory effects in immune responses and constitutes an important target for the development of novel therapeutic drugs against human diseases. Here we describe a new CD28 homologue (CD28H) that has unique functions in the regulation of the human immune response and is absent in mice. CD28H is constitutively expressed on all naive T cells. Repetitive antigenic exposure, however, induces a complete loss of CD28H on many T cells, and CD28H negative T cells have a phenotype of terminal differentiation and senescence. After extensive screening in a receptor array, a B7-like molecule, B7 homologue 5 (B7-H5), was identified as a specific ligand for CD28H. B7-H5 is constitutively found in macrophages and could be induced on dendritic cells. The B7-H5/CD28H interaction selectively costimulates human T-cell growth and cytokine production via an AKT-dependent signalling cascade. Our study identifies a novel costimulatory pathway regulating human T-cell responses.

Original languageEnglish (US)
Article number2043
JournalNature communications
Volume4
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Zhu, Y., Yao, S., Iliopoulou, B. P., Han, X., Augustine, M. M., Xu, H., Phennicie, R. T., Flies, S. J., Broadwater, M., Ruff, W., Taube, J. M., Zheng, L., Luo, L., Zhu, G., Chen, J., & Chen, L. (2013). B7-H5 costimulates human T cells via CD28H. Nature communications, 4, [2043]. https://doi.org/10.1038/ncomms3043