CD5 signal transduction: Positive or negative modulation of antigen receptor signaling

The CD5 lymphocyte surface glycoprotein is a coreceptor involved in the mod ulation of antigen-specific receptor-mediated activation and differentiatio n signals. Although first considered a costimulatory molecule in mature per ipheral T cells, recent studies of CD5(-/-) mice have opened the possibilit y that CD5 may also mediate inhibitory signals that attenuate TCR/CD3- and BCR-mediated triggering in thymocytes and a subgroup of B cells (B-1a cells ), respectively. The ultimate molecular basis for these differential modula tory properties of CD5, depending on the context of lymphocyte subset and d ifferentiation stage, are presently unknown and are an issue of current int ensive investigation. Here, we review recent reports, both contradictory an d complementary, focused on CD5-mediated molecular intracellular signaling events that could provide the basis for its immunomodulatory properties.