Expression of the p56(lck) Y505F mutation in CD45-deficient mice rescues thymocyte development

Mice deficient in the transmembrane protein tyrosine phosphatase CD45 exhib it a block in thymocyte development. To determine whether the block in thym ocyte development was due to the inability to dephosphorylate the inhibitor y phosphorylation site (Y505) in p56(lck) (Lck), we generated CD45-deficien t mice that express transgenes for the Lck Y505F mutation and the DO11.10 T -cell antigen receptor (TCR). CD4 single-positive T cells developed and acc umulated in the periphery. Treatment with antigen resulted in thymocyte apo ptosis and the loss of transgenic-TCR-bearing cells. Peripheral CD45-defici ent T cells from the mice expressing both transgenes responded to antigen b y increasing CD69 expression, interleukin-2 production, and proliferation. These results indicate that thymocyte development requires the dephosphoryl ation of the inhibitory site in Lck by CD45.