B7-H3 is a type I transmembrane protein belonging to the B7 family of co-stimulatory proteins. B7-H3 is mostly expressed on professional APCs including B cells, macrophages, and dendritic cells at low level. It is detected on various human and murine tumor cells, nasal and airway epithelial cells. Its expression on dendritic cells appears to be up-regulated by LPS. Initial studies have shown that B7-H3 provides a stimulatory signal to T cells. However, recent studies suggest a negative regulatory role for B7-H3 in T cell responses. Mouse B7-H3 protein inhibited T cell activation and effector cytokine production. Thus, the immunological function of B7-H3 remains unclear. B7-H3 is involved in the suppression of Th1-mediated immune responses and plays an important role in the development of pathogenic Th2 cells in a murine asthma model. Monoclonal antibody against B7-H3 enhances T cell proliferation in vitro and leads to exacerbated EAE in vivo. It was reported recently that the Triggering Receptor Expressed on Myeloid cells (TREM)-like Transcript 2 (TLT-2, TREML2) is a receptor for B7-H3 in mice. It remains controversial. Further studies are needed to identify the receptor of B7-H3.