Opposing effects of protein tyrosine kinase inhibitors on the monoclonal antibody induced internalization of CD3 and CD4 antigens.

We have previously demonstrated that the monoclonal antibody (mAb)-induced modulation of CD3 and CD4 antigens from the surface of human peripheral blood lymphocytes is not dependent from protein kinase C activity (Thuillier et al., Eur. J. Immunol. 1990. 20:1197). In the present report we study the effect of genistein and of herbimycin A, two potent inhibitors of protein tyrosine kinases (PTK), on the mAb-induced modulation of CD3 and CD4 surface antigens. Both genistein and herbimycin inhibited the mAb-induced internalization of CD3 and, in contrast, facilitated that of CD4 antigen. These results indicate that the mAb-induced modulation of CD3 is essentially dependent on the PTK pathway, whereas PTK appear to negatively regulate the mAb-induced modulation of CD4.