Fyn can partially substitute for Lck in T lymphocyte development

Abstract

Lck, a Src family tyrosine kinase, transduces signals important for the development of alphabeta and gammadelta T cells. However, T cell development is only partially compromised in Lck-deficient mice, suggesting that other kinases may also transduce pre-TCR or TCR signals. One candidate is Fyn, a Src kinase coexpressed with Lck in immature and mature T cells. Here we show that T cell development is completely compromised in lck(-/-)fyn(-/-) mice. In addition, we demonstrate that expression of a gain-of-function mutant fyn(T) transgene completely restores production of immature CD4/CD8 double positive thymocytes and gammadelta T cells and improves the representation of CD4 or CD8 single positive thymocytes. These observations reveal that Fyn can subserve some Lck-like functions in T cell development.