Direct evidence for a two-signal mechanism of cytotoxic T-lymphocyte activation.

The cellular requirements for the activation of cytotoxic T lymphocytes to alloantigens are complex. In addition to cytotoxic precursors (CLPs), metabolically active stimulator cells, adherent accessory (A) cells and antigen-specific helper T cells are also required. However, the requirement for A cells, metabolically active stimulator cells or helper T cells can be replaced by soluble factors or co-stimulator (CoS), a lymphokine obtained by stimulation of murine spleen cells with concanavalin A (Con A). We show here that in the presence of CoS, cultures containing on average one lymph node lymphocyte (LNL) and Con A can be activated to produce single cytotoxic clones. This observation strongly suggests that one of the target cells of CoS is the CLP and provides more direct evidence for a two-signal mechanism for cytotoxic T lymphocyte activation.