Lineage-Specific Control of Superantigen-Induced Cell Death by the Protein Tyrosine Kinase p56^lck

Abstract

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 p56lck in cell death of developing T cells, we introduced endogenous mouse mammary tumor retroviruses encoding superantigens (SAG) into p56lck-deficient mice. We show that clonal deletion of SAG-reactive CD4+ T cells does occur in p56lck -/- mice. Clonal deletion was also evident in CD4+ cells expressing TCRVβ7, which has low affinity for Mls-1a. However, clonal deletion did not occur in SAG-reactive CD8+ T cells from p56lck -/- mice. Deletion of cells expressing SAG-reactive TCRVβ chains was apparent in CD4+ single-positive but not in CD8+ single-positive thymocytes. Both CD4+ and CD8+ peripheral T cells from Mls-1b p56lck -/- mice responded to Mls-1a in vitro. However, CD8+ T cells from Mls-1a p56lck -/- mice that did not undergo deletion could not respond to Mls-1a, indicating that these cells are functionally unresponsive. These data show that p56lck is not required for clonal deletion of SAG-reactive CD4+ lymphocytes, including CD4+ cell expressing TCRs with low affinity for the SAG. However, p56lck appears to be an important signal transduction molecule involved in deletion of SAG-reactive CD8+ T cells.