B7-H5 costimulates human T cells via CD28H

摘要

The B7/CD28 family has profound modulatory effects in immune responses and constitutesan 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 theregulation of the human immune response and is absent in mice. CD28H is constitutivelyexpressed on all naive Tcells. Repetitive antigenic exposure, however, induces a complete lossof CD28H on many T cells, and CD28H negative T cells have a phenotype of terminaldifferentiation and senescence. After extensive screening in a receptor array, a B7-likemolecule, B7 homologue 5 (B7-H5), was identified as a specific ligand for CD28H. B7-H5 isconstitutively found in macrophages and could be induced on dendritic cells. The B7-H5/CD28H interaction selectively costimulates human T-cell growth and cytokine production viaan AKT-dependent signalling cascade. Our study identifies a novel costimulatory pathwayregulating human T-cell responses.