Cytotoxic γδ or αβ T Cells with a Natural Killer Cell Marker, CD56, Induced from Human Peripheral Blood Lymphocytes by a Combination of IL-12 and IL-2

Populations of cytotoxic CD3⁺CD56⁺ cells were selectively expanded when monocyte-depleted human PBL (M(-) PBL) were cultured with 20 U/ml IL-12 and 100 U/ml IL-2. In a majority of cases, CD4^-CD8^- as well as CD8⁺ γδ T cells with CD56 Ag were induced, but in some cases CD4⁺CD56⁺ αβ T cells were selectively increased. Determination of which will increase, 76 or αβ T cells, apparently is dependent upon individuals. When M(-) PBL were stimulated with IL-12 and IL-2 in the presence of immobilized anti-CD3 Ab, CD8⁺CD56⁺ αβ T cells increased exclusively. When M(-) PBL were cultured by IL-2 alone, CD3⁺CD56^- cell expansion was predominant while CD3⁺CD56⁺ cells remained a minor population. Cytotoxic activity of M(-) PBL cultured with a combination of IL-12 and IL-2 is much greater than when cultured with IL-2 alone. The cytotoxicity of activated M(-) PBL was abrogated by the depletion of either CD3⁺ or CD56⁺ cells irrespective of their γδ or αβ phenotypes. These types of cells are preferentially present in the livers of humans. The results revealed that, under certain conditions, IL-12 synergizes with IL-2 to induce potent cytotoxic T cells with CD56 Ag of humans, and suggest that these cells in the human liver are functionally similar to NK1⁺ αβ T cells in murine liver.