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

摘要

This work analyzes the hypothesis that human CD38 may cooper- ate with MHC Class II by acting as coreceptor in a superantigen- induced activation. The initial evidence is that CD38 ligation by specific monoclonal antibodies inhibits superantigen-induced T lymphocyte proliferation. Inhibitory effects become apparent after engagement of CD38 expressed by monocytes. whereas ligation of CD38 expressed by T Iymphocytes does not apparently affect activation. The inhibition requires a cell-to-cell interaction. fol- lowed by the relevant transmembrane signaling that is reproduced by CD38 ligation. Indeed, CD38 ligation on monocytes induces tyrosine phosphorylation of several intracellular proteins including the protooncogene product c-cbl and the fgr and hck tyrosine kinases. The receptorial nature of the CD38-mediated events is confirmed by the observation of an intracellular calcium flux in monocytes secondary to CD38 ligation. These effects are additive with the similar events elicited by MHC Class ll ligation, a likely indication that CD38 and MHC Class ll share a common activation pathway. This conclusion is strengthened by results of comodula- tion experiments. indicating that CD38 and MHC Class lI display lateral associations on monocytes. These results attribute to CD38 expressed by monocytes a role in the transduction of signal(s) involved in superantigen-induced activation, operating in synergy with MHC Class ll.