Lineage-specific control of superantigen-induced cell death by the protein tyrosine kinase p56(lck).
Cell fate decisions in developing T cells depend on signal transduction via the Ag-specific TCR. Although the same TCR can signal for survival or cell death, specific signals that lead to cellular activation or death have not been identified. To study the role of the src tyrosine kinase p56(lck) in cell death of developing T cells, we introduced endogenous mouse mammary tumor retroviruses encoding superantigens (SAG) into p56(lck)-deficient mice. We show that clonal deletion of SAG-reactive CD4+ T cells does occur in p56(lck) -/- mice. Clonal deletion was also evident in CD4+ cells expressing TCRVbeta7, which has low affinity for Mls-1a. However, clonal deletion did not occur in SAG-reactive CD8+ T cells from p56(lck) -/- mice. Deletion of cells expressing SAG-reactive TCRVbeta chains was apparent in CD4+ single-positive but not in CD8+ single-positive thymocytes. Both CD4+ and CD8+ peripheral T cells from Mls-1b p56(lck) -/- mice responded to Mls-1a in vitro. However, CD8+ T cells from Mls-1a p56(lck) -/- mice that did not undergo deletion could not respond to Mls-1a, indicating that these cells are functionally unresponsive. These data show that p56(lck) is not required for clonal deletion of SAG-reactive CD4+ lymphocytes, including CD4+ cell expressing TCRs with low affinity for the SAG. However, p56(lck) appears to be an important signal transduction molecule involved in deletion of SAG-reactive CD8+ T cells.
Penninger
J M
JM
Amgen Institute, Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto, Canada.
Wallace
V A
VA
Molina
T
T
Mak
T W
TW
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016923:Cell Death; D017637:Clonal Deletion; D008198:Lymph Nodes / Q000166:cytology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018089:Superantigens / Q000276:immunology*; D019061:src-Family Kinases / Q000502:physiology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases