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

Abstract

The cellular requirements for the activation of cytotoxic T lymphocytes to alloantigens are complex. In addition to cytotoxic precursors (CLPs), metaholically active stimulator cells¹, adherent accessory (A) cells^2,3 and antigen-specific helper T cells⁴ are also required. However, the requirement for A cells^5,6, metabolically active stimulator cells^1,7,8 or helper T cells⁹ can be replaced by soluble factors or co-stimulator (CoS)¹⁰, 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.