Requirement for natural killer cells in the induction of cytotoxic T cells

Cell-mediated immunity involves the participation of both regulatory and cytotoxic cells. The conversion of precursors to effector CD8⁺ cytotoxic T (Tc) cells requires cell-cell collaboration in which CD4⁺ T cells are traditionally viewed as helper cells. An in vitro system was used here to demonstrate that the generation of human alloantigen-specific CD8⁺ Tc cells requires the participation of CD3^-CD16⁺CD56⁺ NK cells but not CD4⁺ T helper cells. Depletion of NK cells from responders abolished the induction of alloantigen-specific Tc cells in mixed lymphocyte cultures (MLC). Purified CD5⁺CD8⁺ T cells stimulated with alloantigen proliferated but did not differentiate into fully functional effector Tc cells. Coculture of responder CD5⁺CD8⁺ T cells with NK cells promoted the conversion of CD8⁺ Tc cell precursors (pTc) into effector Tc cells. Anti-CD56 mAbs blocked Tc cell induction in MLC, suggesting a role for CD56 molecules expressed on NK cells in either alloantigen recognition or delivery of accessory signals to pTc cells. These findings suggest a novel critical link between the natural and specific immune responses.