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 transductio n via the Ag-specific TCR. Although the same TCR can signal for surviv al 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 en dogenous mouse mammary tumor retroviruses encoding superantigens (SAG) into p56(lck)-deficient mice. We show that clonal deletion of SAG-rea ctive CD4(+) T cells does occur in p56(lck) -/- mice, Clonal deletion was also evident in CD4(+) cells expressing TCRV beta 7, which has low affinity for Mls-1(a). However, clonal deletion did not occur in SAG- reactive CD8(+) T cells from p56(lck) -/- mice. Deletion of cells expr essing SAG-reactive TCRV beta chains was apparent in CD4(+) single-pos itive but not in CD8(+) single-positive thymocytes. Both CD4(+) and CD 8(+) peripheral T cells from Mls-1(b) p56(lck) -/- mice responded to M ls-1(a) in vitro. However, CD8(+) T cells from Mls-1(a) p56(lck) -/- m ice that did not undergo deletion could not respond to Mls-1(a), indic ating 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 affinit y for the SAG, However, p56(lck) appears to be an important signal tra nsduction molecule involved in deletion of SAG-reactive CD8(+) T cells .