ALTERATIONS IN THE LEVEL OF CD45 SURFACE EXPRESSION AFFECT THE OUTCOME OF THYMIC SELECTION

CD45 is a receptor protein tyrosine phosphatase whose activity is requ ired for thymocyte development and TCR-mediated signal transduction. H ere we show that positive selection of TCR-alpha beta transgenic thymo cytes is completely blocked in CD45 exon 6 -/- gene-deficient (CD45 -/ -) mice that express the P14 TCR specific for the lymphocytic choriome ningitis virus. Thymocytes from mice heterozygous for the targeted dis ruption of the CD45 gene (CD45 +/-) displayed a reduction in both CD45 surface intensity and enzymatic CD45 protein tyrosine phosphatase act ivity. Surprisingly, positive thymocyte selection was enhanced in CD45 +/- mice as characterized by an up-regulation of the P14 TCR on thymo cytes and increased numbers of transgenic T cells. Using a variant of lymphocytic choriomeningitis virus that is impaired in the induction o f negative selection of P14 thymocytes, we also show that the reductio n of CD45 surface expression in CD45 +/- mice rendered P14 transgene t hymocytes susceptible to negative selection. These data demonstrate th at changes in the expression level of the receptor protein tyrosine ph osphatase CD45 can alter thymic selection.