[PDF][PDF] αβ T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases

NSC Van Oers, B Lowin-Kropf, D Finlay, K Connolly… - Immunity, 1996 - cell.com
NSC Van Oers, B Lowin-Kropf, D Finlay, K Connolly, A Weiss
Immunity, 1996cell.com
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 …
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 CD4CD8 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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