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Molecular and Cellular Biology, June 1999, p. 4200-4208, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Expression of the p56lck Y505F Mutation in CD45-Deficient Mice Rescues Thymocyte Development

John R. Seavitt,1 Lynn S. White,1 Kenneth M. Murphy,1 Dennis Y. Loh,2 Roger M. Perlmutter,3 and Matthew L. Thomas1,*

Center for Immunology, Department of Pathology and Howard Hughes Medical Institute, Washington University, St. Louis, Missouri 631101; Hoffmann-LaRoche, Nutley, New Jersey 071102; and Merck & Co., Rahway, New Jersey 070653

Received 19 January 1999/Returned for modification 23 February 1999/Accepted 23 March 1999

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 p56lck (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.

* Corresponding author. Mailing address: Department of Pathology and Howard Hughes Medical Institute, Washington University, Campus Box 8118, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-8722. Fax: (314) 362-8888. E-mail: mthomas{at}pathbox.wustl.edu.

Molecular and Cellular Biology, June 1999, p. 4200-4208, Vol. 19, No. 6
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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