TCR signals mediated by Src family kinases are essential for the survival of naive T cells.
The role of TCR signals triggered by recognition of self MHCs in maintaining the survival of naive peripheral T cells remains controversial. Here we examine the role of the Src family kinases, p56(lck) (Lck) and p59(fyn) (Fyn), in the survival of naive T cells. We show that long term survival requires a combination of signals transduced by Src family kinases and signals through the IL-7R. In the absence of either one, naive T cells die slowly, but if both signals are removed, cell loss is greatly accelerated. The TCR signal can be mediated by either Fyn or Lck at wild-type levels of expression, but not by Lck alone if expressed suboptimally. The disappearance of T cells in the absence of Fyn and Lck was associated with a complete loss of TCRzeta-chain phosphorylation and down-regulation of CD5, both of which are also MHC contact dependent, indicating that the Src family kinases are critical for transducing a TCR-MHC survival signal.
Seddon
Benedict
B
Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, London, United Kingdom.
Zamoyska
Rose
R
D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D018956:CD5 Antigens / Q000096:biosynthesis; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D004357:Drug Synergism; D015971:Gene Expression Regulation, Enzymologic / Q000276:immunology; D007399:Interphase / Q000235:genetics / Q000276:immunology; D018655:Lymphocyte Count; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism / Q000502:physiology*; D020395:Receptors, Interleukin-7 / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D019076:Transgenes / Q000276:immunology; D019061:src-Family Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D018956:CD5 Antigens; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D020395:Receptors, Interleukin-7; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases