AN ACTIVATED LCK TRANSGENE PROMOTES THYMOCYTE DEVELOPMENT IN RAG-1 MUTANT MICE

Expression of the T cell receptor P (TCR beta) chain is necessary for the transition from the CD4(-)CD8(-) stage in the major alpha beta thymocyte lineage. The protein tyrosine kinase p56(lck) has been implicated in the regulation of early thymocyte differentiation and of allelic exclusion at the TCR beta locus. Using mice overexpressing an activated lck transgene and mice with a disruption of the lck gene, we demonstrate that p5(lck) participates in a pathway that regulates the expansion of the pool of CD4(+)CD8(+) thymocytes to wild-type levels. In addition, p56(lck) may be involved in the down-regulation of the putative pre-TCR on CD4(+)CD8(+) thymocytes.