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 hematopoletlc 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 fall to proliferate in response to antigen or cross-linked CD3. These studies have now been extended to show that stimulation with antl-Thy-1, a mltogenlc 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 cells correlates antl-Thy-1 unresponslveness with a failure to increase in tyrosine phosphorylatlon. Furthermore, stimulation of CD8+CD45+ T cells with antl-Thy-1 results in an increase in p56ick activity but not in CD8+CD45− T cells. In contrast to the results with antl-Thy-1, both the CD4+− CD45 and CD8+CD45− T cells respond to treatment with lectin mitogens, concanavalln A or phytohemagglutlnln. Lectin-lnduced proliferation was inhibited by the addition of cyclosporln A. Treatment of CD45− T cells with PMA and lonomycln also results in proliferation indicating that activation of protein kinase C in conjunction with an increase in intracellular calcium rescues the defect cafsed by CD45 deficiency. The data suggest that CD45 Is required for the activation of tyrosine kinase activity Immediate or prior to transmembrane signaling.