ENGAGEMENT OF THE EXTERNAL DOMAINS OF CD45 TYROSINE PHOSPHATASE CAN REGULATE THE DIFFERENTIATION OF IMMATURE CD4-CELLS(CD8+ THYMOCYTES INTOMATURE T)

Immature precursor cells are induced in the thymus to express clonotyp ic T-cell antigen receptors (TCRs) and to differentiate into mature T cells. Perhaps the least understood event which occurs during intrathy mic development is the positive selection of immature CD4(+)CD8(+) thy mocytes for differentiation into mature CD4(+) and CD8(+) T cells base d on the TCR specificity individual thymocytes express. TCR expression by CD4(+)CD8(+) thymocytes is quantitatively regulated by CD4-mediate d activation of p56(lck) protein-tyrosine kinase whose activity can in turn be regulated by the membrane-bound protein-tyrosine-phosphatase CD45. Here we show that antibody engagement of CD45 external domains e nhances Lck tyrosine kinase activity in CD4(+)CD8(+) thymocytes, inhib its TCR expression, and inhibits differentiation of immature CD4(+)CD8 (+) thymocytes into mature T cells. Thus, engagement of the external d omains of CD45 tyrosine phosphatase can regulate the ability of immatu re CD4(+)CD8(+) thymocytes to undergo positive selection, suggesting a n important regulatory role for intrathymic ligands that are capable o f engaging CD45 within the thymus.