Thymic CD45 tyrosine phosphatase regulates apoptosis and MHC-restricted negative selection.
The acquisition of immunologic self-tolerance is governed, in part, by selection mechanisms that occur during intrathymic T cell ontogeny. Although considerable data exist for the molecular basis of mature T cell signal transduction, the enzymes that participate in thymic TCR selection processes have remained unidentified. We report that augmented thymic expression of the CD45R0 protein tyrosine phosphatase increased the efficacy of TCR-mediated apoptosis and MHC-restricted negative selection of HY TCRs in vivo. Additionally, augmented CD45R0 expression resulted in the activation of endogenous p56lck tyrosine kinase in CD4+CD8+ thymocytes. These results identify a cellular enzyme, the CD45R0 protein tyrosine phosphatase, involved in the regulation of apoptosis and TCR selection mechanisms during CD4+CD8+ thymocyte differentiation.
Ong
C J
CJ
Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Chui
D
D
Teh
H S
HS
Marth
J D
JD
D000818:Animals; D017209:Apoptosis; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008285:Major Histocompatibility Complex; D051379:Mice; D008822:Mice, Transgenic; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000201:enzymology / Q000276:immunology
D011948:Receptors, Antigen, T-Cell; D011505:Protein-Tyrosine Kinases; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases