Lck dependence of signaling pathways activated by gamma-irradiation and CD3 epsilon engagement in RAG-1(-/-)-immature thymocytes

Abstract

The src family tyrosine kinase, Lck, transduces signals from the pre-TCR complex which regulate the development and expansion of CD4/CD8 double-positive (DP) thymocytes from CD25(+) CD4/CD8 double-negative progenitors. We and others have recently shown that sublethal gamma-irradiation bypasses the need for TCRbeta expression to promote the development and expansion of DP thymocytes in scid or recombinase-activating gene (RAG)-deficient mice. Here we demonstrate that gamma-irradiation activates an Lck-dependent signaling process in immature thymocytes similar to that initiated physiologically by the pre-TCR complex.