Abstract
Two families of protein tyrosine kinases (PTKs), the Src and Syk/ZAP-70 families, are required for T cell development. Lck is the major Src family member required for thymopoiesis, since there is a severe deficit of CD4 +CD8 + thymocytes and mature T cells in its absence. However, some peripheral T cells are evident in these mice, suggesting that additional PTKs may contribute to T cell development. Here we show that the combined disruption of Lck and Fyn ( lck −/− fyn −/−) completely arrests αβ T cell development at the CD4 −CD8 − stage. The development of Vγ3 + dendritic epidermal T cells is also severely impaired, but natural killer cell development and cytolytic activity is unaffected in lck −/− fyn −/− mice. These findings reveal the potential for redundant functions mediated by Src family PTKs while emphasizing crucial roles for Lck and Fyn in T cell development.
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