Engagement of the external domains of CD45 tyrosine phosphatase can regulate the differentiation of immature CD4⁺CD8⁺ thymocytes into mature T cells

Immature precursor cells are induced in the thymus to express clonotypic T-cell antigen receptors (TCRs) and to differentiate into mature T cells. Perhaps the least understood event which occurs during intrathymic development is the positive selection of immature CD4⁺CD8⁺ thymocytes for differentiation into mature CD4⁺ and CD8⁺ T cells based on the TCR specificity individual thymocytes express. TCR expression by CD4⁺CD8⁺ thymocytes is quantitatively regulated by CD4-mediated 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 enhances Lck tyrosine kinase activity in CD4⁺CD8⁺ thymocytes, inhibits TCR expression, and inhibits differentiation of immature CD4⁺CD8⁺ thymocytes into mature T cells. Thus, engagement of the external domains of CD45 tyrosine phosphatase can regulate the ability of immature CD4⁺CD8⁺ thymocytes to undergo positive selection, suggesting an important regulatory role for intrathymic ligands that are capable of engaging CD45 within the thymus.