Greatly reduced efficiency of both positive and negative selection of thymocytes in CD45 tyrosine phosphatase-deficient mice.
The T cell repertoire is shaped by positive and negative selection of thymocytes. TCR-mediated signals that determine these selection processes are only partly understood. The CD45 tyrosine phosphatase has been shown to be important for signal transduction through the TCR, but there has been disagreement about whether CD45 is a positive or negative regulator of TCR signaling. Using CD45-deficient mice expressing transgenic TCR, we show that in the absence of CD45 there is a large increase in the thresholds of TCR stimulation required for both positive and negative selection. Our results conclusively demonstrate that in double-positive thymocytes CD45 is a positive regulator of the TCR signals that drive thymic selection events.
Mee
P J
PJ
National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK.
Turner
M
M
Basson
M A
MA
Costello
P S
PS
Zamoyska
R
R
Tybulewicz
V L
VL
D000818:Animals; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D018390:Gene Targeting / Q000379:methods; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D017027:Protein Tyrosine Phosphatases / Q000172:deficiency*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013234:Stem Cells / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D017493:Leukocyte Common Antigens; D017027:Protein Tyrosine Phosphatases; D002118:Calcium