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

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