Dendritic cells are targets for human invariant Vα24+ natural killer T-cell cytotoxic activity: An important immune regulatory function

Objective Human invariant Vα24+ natural killer T (NKT) cells, a subpopulation of NK cell-receptor (NKR-P1A)-expressing T cells with an invariant Vα24JαQ T-cell receptor (TCR), are stimulated by the glycolipid a-galactosylceramide (KRN7000), in a CD1d-dependent, TCR-mediated fashion. Little is known about invariant Vα24+ NKT cell function or mechanisms of effector activity. Evidence suggests this cell population protects against autoimmunity and has antitumor effects against leukemia and solid tumors. Materials and Methods We compared the phenotype and function of invariant Vα24+ NKT cells, from patients with chronic myeloid leukemia (CML) and normal donors, generated by stimulation of peripheral blood mononuclear cells with α-galactosylceramide pulsed monocyte-derived dendritic cells. The CD4−CD8− (double negative) population was studied further. Results Activated human invariant Vα24+ NKT cells were cytotoxic against autologous and allogeneic peripheral blood dendritic cells and monocyte-derived dendritic cells but not against autologous or allogeneic T-cell PHA blasts, B-cell lymphoblastoid cell lines, monocytes, or leukemic cells from patients with CML. The findings are consistent with previous observations showing the importance of CD1d in target cell recognition. None of the Vα24+ NKT cell lines expressed the NK markers CD16, CD56, CD94, or killer inhibitory receptors, but all expressed NKR-P1A. There was no difference in phenotype, function, or ease of generation of invariant Vα24+ NKT cells between normal donors and patients with CML. Conclusion Based on our results and the previous evidence linking reduced Vα24+ NKT cells to autoimmunity, we propose that double-negative Vα24+ NKT cells have important immune regulatory functions, including contribution to the prevention of excessive antigen stimulation by virtue of cytotoxic activity against antigen presenting cells, particularly in dendritic cells.