Programming for cytotoxic effector function occurs concomitantly with CD4 extinction during CD8+ T cell differentiation in the thymus

CD4(+) T cells are generally specialized to function as helper cells and CD8(+) T cells are generally specialized to function as cytotoxic effector cells. To explain how such concordance is achieved between co-receptor expression and immune function, we considered two possibilities. In one case, immature CD4(+)CD8(+) thymocyte precursors might first down-regulate expression of one co-receptor molecule, with the remaining co-receptor molecule subsequently activating the appropriate helper or cytotoxic functional program. Alternatively, we considered that the same intrathymic signals that selectively extinguished expression of one or the other co-receptor molecule might simultaneously initiate the appropriate helper or cytotoxic functional program. In the present study, we attempted to distinguish between these alternatives by examining thymocyte precursors of CD8(+) T cells for expression of Cathepsin C and Cathepsin W, molecules important for cytotoxic effector function. We report in developing thymocytes that Cathepsin C and Cathepsin W are expressed coordinately with extinction of CD4 co-receptor expression. We conclude that CD4 extinction and initiation of the cytotoxic functional program occurs simultaneously during differentiation of CD8(+) T cells in the thymus.