ACTIVATION OF CD45-DEFICIENT T-CELL CLONES BY LECTIN MITOGENS BUT NOTANTI-THY-1

CD45, the leukocyte-common antigen, is a transmembrane protein tyrosin e phosphatase uniquely expressed by cells of hematopoietic origin. We have developed CD4+ and CD8+ T cell clones that are deficient in the e xpression of CD45 and have previously shown that these cells fall to p roliferate in response to antigen or cross-linked CD3. These studies h ave now been extended to show that stimulation with anti-Thy-1, a mito genic signal for the CD4+CD45+ and CD8+CD45+ T cells, falls to induce proliferation in the CD45- T cells. Examination of the CD8+CD45- T cel ls correlates anti-Thy-1 unresponsiveness with a failure to increase i n tyrosine phosphorylation. Furthermore, stimulation of CD8+CD45+ T ce lls with anti-Thy-1 results in an increase in p56lck activity but not in CD8+CD45- T cells. In contrast to the results with anti-Thy-1, both the CD4+CD45- and CD8+CD45- T cells respond to treatment with lectin mitogens, concanavalin A or phytohemagglutinin. Lectin-induced prolife ration was inhibited by the addition of cyclosporin A. Treatment of CD 45- T cells with PMA and ionomycin also results in proliferation indic ating that activation of protein kinase C in conjunction with an incre ase in intracellular calcium rescues the defect caused by CD45 deficie ncy. The data suggest that CD45 is required for the activation of tyro sine kinase activity immediate or prior to transmembrane signaling.