Systematic characterization of human CD8 + T cells with natural killer cell markers in comparison with natural killer cells and normal CD8 + T cells

Summary We investigated the function of CD56 +  CD8 + T cells (CD56 + T cells) and CD56 −  CD57 +  CD8 + T cells (CD57 + T cells; natural killer (NK)‐type T cells) and compared them with those of normal CD56 −  CD57 −  CD8 + T cells (CD8 + T cells) and CD56 + NK cells from healthy volunteers. After the stimulation with immobilized anti‐CD3 antibodies, both NK‐type T cells produced much larger amounts of interferon‐γ (IFN‐γ) than CD8 + T cells. Both NK‐type T cells also acquired a more potent cytotoxicity against NK‐sensitive K562 cells than CD8 + T cells while only CD56 + T cells showed a potent cytotoxicity against NK‐resistant Raji cells. After the stimulation with a combination of interleukin (IL)‐2, IL‐12 and IL‐15, the IFN‐γ amounts produced were NK cells ≥ CD56 + T cells ≥ CD57 + T cells > CD8 + T cells. The cytotoxicities against K562 cells were NK cells > CD56 + T cells ≥ CD57 + T cells > CD8 + T cells while cytotoxicities against Raji cells were CD56 + T cells > CD57 + T cells ≥ CD8 + T cells ≥ NK cells. However, the CD3‐stimulated proliferation of both NK‐type T cells was smaller than that of CD8 + T cells partly because NK‐type T cells were susceptible to apoptosis. In addition to NK cells, NK‐type T cells but not CD8 + T cells stimulated with cytokines, expressed cytoplasmic perforin and granzyme B. Furthermore, CD3‐stimulated IFN‐γ production from peripheral blood mononuclear cells (PBMC) correlated with the proportions of CD57 + T cells in PBMC from donors. Our findings suggest that NK‐type T cells play an important role in the T helper 1 responses and the immunological changes associated with ageing.