Dendritic cells are targets for human invariant V alpha 24+natural killer T-cell cytotoxic activity: An important immune regulatory function

Objective. Human invariant V alpha 24+ natural killer T (NKT) cells, a subp opulation of NK cell-receptor (NKR-P1A)-expressing T cells with an invarian t V alpha 24J alpha Q T-cell receptor (TCR), are stimulated by the glycolip id alpha-galactosylceramide (KRN7000), in a CD1d-dependent, TCR-mediated fa shion. Little is known about invariant V alpha 24+ NKT cell function or mec hanisms of effector activity. Evidence suggests this cell population protec ts against autoimmunity and has antitumor effects against leukemia and soli d tumors. Materials and Methods. We compared the phenotype and function of invariant V alpha 24+ NKT cells, from patients with chronic myeloid leukemia (CML) an d normal donors, generated by stimulation of peripheral blood mononuclear c ells with alpha-galactosylceramide pulsed monocyte-derived dendritic cells. The CD4(-)CD8(-) (double negative) population was studied further. Results. Activated human invariant V alpha 24+ NKT cells were cytotoxic aga inst autologous and allogeneic peripheral blood dendritic cells and monocyt e-derived dendritic cells but not against autologous or allogeneic T-cell P HA blasts, B-cell lymphoblastoid cell lines, monocytes, or leukemic cells f rom patients,vith CML. The findings are consistent with previous observatio ns showing the importance of CD1d in target cell recognition. None of the V alpha 24+ NKT fell lines expressed the NK markers CD16, CD56, CD94, or kil ler inhibitory receptors, but all expressed NKR-P1A. There was no differenc e in phenotype, function, or ease of generation of invariant V alpha 24+ NK T cells between normal donors and patients with CML. Conclusion. Based on our results and the previous evidence linking reduced V alpha 24+ NKT cells to autoimmunity, we propose that double-negative V al pha 24+ NKT cells have important immune regulatory functions, including con tribution to the prevention of excessive antigen stimulation by virtue of c ytotoxic activity against antigen presenting cells, particularly in dendrit ic cells. (C) 2000 International Society for Experimental Hematology. Publi shed by Elsevier Science Inc.