CD38 expressed on human monocytes: A coaccessory molecule in the superantigen-induced proliferation

This work analyzes the hypothesis that human CD38 may cooperate with MHC Cl ass II by acting as coreceptor in a superantigen-induced activation. The in itial evidence is that CD38 ligation by specific monoclonal antibodies inhi bits superantigen-induced T lymphocyte proliferation. Inhibitory effects be come apparent after engagement of CD38 expressed by monocytes, whereas liga tion of CD38 expressed by T lymphocytes does not apparently affect activati on, The inhibition requires a cell-to-cell interaction, followed by the rel evant transmembrane signaling that is reproduced by CD38 ligation. Indeed, CD38 ligation on monocytes induces tyrosine phosphorylation of several intr acellular proteins including the protooncogene product c-cbl and the fgr an d hck tyrosine kinases, The receptorial nature of the CD38-mediated events is confirmed by the observation of an intracellular calcium flux in monocyt es secondary to CD38 ligation. These effects are additive with the similar events elicited by MHC Class II ligation, a likely indication that CD38 and MHC Class II share a common activation pathway. This conclusion is strengt hened by results of comodulation experiments, indicating that CD38 and MHC Class II display lateral associations on monocytes, These results attribute to CD38 expressed by monocytes a role in the transduction of signal(s) inv olved in superantigen-induced activation, operating in synergy with MHC Cla ss II.