Expression of the p56lck Y505F Mutation in CD45-Deficient Mice Rescues Thymocyte Development |
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Authors: | John R. Seavitt Lynn S. White Kenneth M. Murphy Dennis Y. Loh Roger M. Perlmutter Matthew L. Thomas |
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Affiliation: | Center for Immunology, Department of Pathology and Howard Hughes Medical Institute, Washington University, St. Louis, Missouri 63110, USA. |
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Abstract: | Mice deficient in the transmembrane protein tyrosine phosphatase CD45 exhibit a block in thymocyte development. To determine whether the block in thymocyte development was due to the inability to dephosphorylate the inhibitory phosphorylation site (Y505) in p56(lck) (Lck), we generated CD45-deficient 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 accumulated in the periphery. Treatment with antigen resulted in thymocyte apoptosis and the loss of transgenic-TCR-bearing cells. Peripheral CD45-deficient T cells from the mice expressing both transgenes responded to antigen by increasing CD69 expression, interleukin-2 production, and proliferation. These results indicate that thymocyte development requires the dephosphorylation of the inhibitory site in Lck by CD45. |
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