Alterations in the level of CD45 surface expression affect the outcome of thymic selection.
CD45 is a receptor protein tyrosine phosphatase whose activity is required for thymocyte development and TCR-mediated signal transduction. Here we show that positive selection of TCR-alphabeta transgenic thymocytes is completely blocked in CD45 exon 6 -/- gene-deficient (CD45 -/-) mice that express the P14 TCR specific for the lymphocytic choriomeningitis virus. Thymocytes from mice heterozygous for the targeted disruption of the CD45 gene (CD45 +/-) displayed a reduction in both CD45 surface intensity and enzymatic CD45 protein tyrosine phosphatase activity. Surprisingly, positive thymocyte selection was enhanced in CD45 +/- mice as characterized by an up-regulation of the P14 TCR on thymocytes and increased numbers of transgenic T cells. Using a variant of lymphocytic choriomeningitis virus that is impaired in the induction of negative selection of P14 thymocytes, we also show that the reduction of CD45 surface expression in CD45 +/- mice rendered P14 transgene thymocytes susceptible to negative selection. These data demonstrate that changes in the expression level of the receptor protein tyrosine phosphatase CD45 can alter thymic selection.
Wallace
V A
VA
Department of Medical Biophysics, University of Toronto, Ontario, Canada.
Penninger
J M
JM
Kishihara
K
K
Timms
E
E
Shahinian
A
A
Pircher
H
H
Kündig
T M
TM
Ohashi
P S
PS
Mak
T W
TW
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D017493:Leukocyte Common Antigens / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000821:virology
D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases