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 CD 8(+) T cells are generally specialized to function as cytotoxic effector ce lls. To explain how such concordance is achieved between co-receptor expres sion and immune function, we considered two possibilities. In one case, imm ature CD4(+)CD8(+) thymocyte precursors might first down-regulate expressio n of one co-receptor molecule, with the remaining co-receptor molecule subs equently activating the appropriate helper or cytotoxic functional program. Alternatively, we considered that the same intrathymic signals that select ively extinguished expression of one or the other co-receptor molecule migh t simultaneously initiate the appropriate helper or cytotoxic functional pr ogram. In the present study, we attempted to distinguish between these alte rnatives 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 Cathepsi n W are expressed coordinately with extinction of CD4 co-receptor expressio n. We conclude that CD4 extinction and initiation of the cytotoxic function al program occurs simultaneously during differentiation of CD8(+) T cells i n the thymus.