Activation of CD45-deficient T cell clones by lectin mitogens but not anti-Thy-1.

CD45, the leukocyte-common antigen, is a transmembrane protein tyrosine phosphatase uniquely expressed by cells of hematopoietic origin. We have developed CD4+ and CD8+ T cell clones that are deficient in the expression of CD45 and have previously shown that these cells fail to proliferate in response to antigen or cross-linked CD3. These studies have now been extended to show that stimulation with anti-Thy-1, a mitogenic signal for the CD4+CD45+ and CD8+CD45+ T cells, fails to induce proliferation in the CD45- T cells. Examination of the CD8+CD45- T cells correlates anti-Thy-1 unresponsiveness with a failure to increase in tyrosine phosphorylation. Furthermore, stimulation of CD8+CD45+ T cells 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 proliferation was inhibited by the addition of cyclosporin A. Treatment of CD45- T cells with PMA and ionomycin also results in proliferation indicating that activation of protein kinase C in conjunction with an increase in intracellular calcium rescues the defect caused by CD45 deficiency. The data suggest that CD45 is required for the activation of tyrosine kinase activity immediate or prior to transmembrane signaling.