EVIDENCE FOR A CD4-ASSOCIATED CALCIUM INFLUX INDEPENDENT OF THE PHOSPHOINOSITIDE TRANSDUCTION PATHWAY IN HUMAN T-CELLS

We recently showed, using human Jurkat T cell variants lacking the T c ell receptor (TCR)/CD3 complex, that the lectin jacalin is able to tri gger intracellular calcium increase provided that CD4 is expressed on the cell surface. Involvement of the CD4 molecule in jacalin-induced b iological effects was furthermore demonstrated in differentiated U937 myelomonocytic cells expressing or not expressing CD4, and is confirme d here in human CD3-transfected mouse thymoma cells. In the present pa per, we analyze the CD4-associated calcium response triggered by jacal in independently of the TCR/CD3 complex. We show that the observed cal cium rise results from a direct long-lasting calcium influx from the o utside without release of calcium from intracellular stores. We demons trate that it is independent of the phosphoinositide phospholipase C t ransduction pathway. Moreover, we show that this peculiar calcium resp onse can be blocked by protein tyrosine kinase inhibitors (herbimycin and genistein) giving evidence of the involvement of a protein tyrosin e kinase, the best candidate of which is the CD4-associated p56(lck). Altogether, our results suggest that, independently of the TCR/CD3 com plex, CD4 may be involved in the triggering of a calcium signal depend ent, on a protein tyrosine kinase and independent of the phosphoinosit ide transduction pathway.