Analysis of Human Va24 CD4 NKT Cells Activated by a-Glycosylceramide-Pulsed Monocyte-Derived Dendritic Cells

Human Va24 NKT cells with an invariant TCR (Va24-JaQ) have been shown to be specifically activated by synthetic glycolipids such as a-galactosylceramide and a-glucosylceramide in a CD1d-restricted and Va24 TCR-mediated manner. We recently characterized Va24 CD4 CD8 double negative (DN) NKT cells using a-galactosylceramide-pulsed monocyte-derived dendritic cells. Here, we compare Va24 CD4 NKT cells with human Va24 DN NKT cells from the same donor using a-galactosylceramide-pulsed monocyte-derived dendritic cells. Human Va24 CD4 NKT cells were phenotypically and functionally similar to the human Va24 DN NKT cells characterized previously. Both of them use Va24-JaQ-Vb11 TCR and express CD161 (NKRP1A), but not the other NK receptors tested so far. They also produce cytokines such as IL-4 and IFN-g, and, in regard to IL-4 production, Va24 CD4 NKT cells produce more IL-4 than Va24 DN NKT cells. The cells exhibit marked cytotoxic activity against the U937 tumor cell line, but not against the NK target cell line, K562. Although at least some of the factors responsible for the stimulation of Va24 NKT cells have been clarified, little is known regarding the killing phase of these cells. Here we show that the cytotoxic activity of Va24 NKT cells against U937 cells is mediated mainly through the perforin pathway and that ICAM-1/LFA-1 as well as CD44/hyaluronic acid interactions are important for the effector phase of Va24 NKT cell-mediated cytotoxicity against U937 cells. The Journal of Immunology, 2000, 164: 4458–4464.