Positive and negative selection of thymocytes depends on Lck interaction with the CD4 and CD8 coreceptors

Considerable evidence supports a role for the Src family protein tyrosine k inase Lck in regulating multiple aspects of thymocyte development. In this report, we establish that early events in T lymphopoiesis are restored to L ck-deficient mice by provision of a transgene encoding a version of Lck tha t cannot interact with the coreceptors CD4 and CD8. In addition, we demonst rate that later events in thymocyte development, specifically, the processe s of positive and negative selection, are compromised in mire where the onl y Lck available cannot associate with either CD4 or CD8. We conclude that n ot only is Lck activity required for positive and negative selection, but t hat that activity must be coupled to the CD4 and CD8 coreceptors.