ALPHA-BETA-T-CELL DEVELOPMENT IS ABOLISHED IN MICE LACKING BOTH LCK AND FYN PROTEIN-TYROSINE KINASES

Two families of protein tyrosine kinases (PTKs), the Src and Syk/ZAP-7 0 families, are required for T cell development. Lck is the major Src family member required for thymopoiesis, since there is a severe defic it of CD4(+)CD8(+) thymocytes and mature T cells in its absence. Howev er, some peripheral T cells are evident in these mice, suggesting that additional PTKs may contribute to T cell development. Here we show th at the combined disruption of Lck and Fyn (lck(-/-)fyn(-/-)) completel y arrests alpha beta T cell development at the CD4(-)CD8(-) stage. The development of V gamma 3(+) dendritic epidermal T cells is also sever ely impaired, but natural killer cell development and cytolytic activi ty is unaffected in lck(-/-)fyn(-/-) mice. These findings reveal the p otential for redundant functions mediated by Src family PTKs while emp hasizing crucial roles for Lck and Fyn in T cell development.