CD97 was identified as an early activation marker on T cells, having low expression on naive T cells. This is a common feature of molecules that have a role in T-cell function. It was subsequently identified as a ligand for CD55, which has been previously identified as an innate regulator of complement. The interaction of this receptor-ligand pair has been shown to provide a potent costimulatory signal to human T cells, despite their modest affinity. Though both CD97 and CD55 are expressed on T cells as well as antigen presenting cells (APCs), their interaction is significant when CD97 on APCs interacts with CD55 on T cells. The converse interaction is poorly defined and may be less significant. A unique aspect of the interaction of CD97 with CD55 is the stimulation of naive T cells, leading to the induction of IL-10 producing cells that behave like Trl regulatory cells. This raises a number of questions regarding the dual functions of CD55; regulating complement and stimulating T cells via CD97 interaction and any potential overlap in the consequences of these dual roles.