Adhesion mediated by LFA‐1 is required for efficient IL‐12‐induced NK and NKT cell cytotoxicity

Interleukin 12 (IL‐12)‐activated NK1.1+TCRα β+ (NKT2) and NK1.1+TCRα β– (NK) cells exhibit cytotoxic activity against a wide variety of tumor cells in the absence of prior sensitization. Here we demonstrate that the integrin adhesion receptor LFA‐1 (CD11a / CD18) regulates the cytotoxic activity of IL‐12‐activated NKT and NK cells against YAC‐1 and EL‐4 tumor cells. Differentiation in vivo and the expression of the cytolytic effector molecules perforin and Fas‐L were comparable in both IL‐12‐activated NKT and NK cells from LFA‐1– / – and LFA‐1+ / + mice. However, LFA‐1– / – IL‐12‐activated NKT and NK cells showed impaired conjugate formation with target cells. These results provide the first genetic evidence for a role for an adhesion receptor in killing by IL‐12‐activated NK cells.