B7-H5 costimulates human T cells via CD28H

نویسندگان

  • 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
چکیده

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.

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عنوان ژورنال:

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2013