Citation

3928 total record number 199 records this year

B7-H5 costimulates human T cells via CD28H.

Zhu, Y;Yao, S;Iliopoulou, BP;Han, X;Augustine, MM;Xu, H;Phennicie, RT;Flies, SJ;Broadwater, M;Ruff, W;Taube, JM;Zheng, L;Luo, L;Zhu, G;Chen, J;Chen, L;

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.