These molecules could be loosely categorized into two distinct types, costimulatory or coinhibitory molecules, based on their functions in regulating T cell responses. Therefore, integrating the functional outcome of costimulatory and coinhibitory interactions determines the fate of a T cell Probenecid response, which leads to response, unresponsiveness, and death. Various cell surface signaling molecules have been identified and characterized, including those in the immunoglobulin IMD 0354 superfamily and the tumor necrosis factor receptor and ligand superfamily. The roles of these receptors and ligands in the positive and negative control of T cell immunity and human disease, including autoimmune diseases, have been firmly established. In 2001, our laboratory initially identified B7-H3 as a costimulatory molecule that promotesan in vitro T cell response. B7-H3 mRNA has been found in human liver, lung, bladder, testis, prostate, breast, and placenta, suggesting that B7-H3 may participate in organ-specific inflammation and auto immune diseases. The counter-receptor for the costimulatory effect of B7-H3 was reported to be myeloid cell-like transcript 2 factor where as other study did not support this finding. Similar to other B7 family homologues, B7-H3 has a single IgV- and IgC-like domain with a transmembrane and intracellular tail in humans, mice, and other species. In humans, a duplicate of the classic B7-H3 was also identified, but the physiological differences between the 2Ig and 4Ig form have yet to be elucidated. The role of endogenous B7-H3 in the pathogenesis and progression of autoimmune disease has been evaluated by various laboratories using both monoclonal antibodies and B7-H3 deficient mice, but the results are somewhat contradictory with both costimulatory and coinhibitory effects being described in various model systems. One interpretation for these contradicting results is that B7-H3 plays a differential role in the regulation of distinct T cell subsets. Therefore, the effect of B7-H3 would be determined by the dominance or bias of T cell subsets in each system or disease status.