In this study, we examine whether recognition of alpha-GalCer presented on CD1d-expressing DCs and B cells in vivo elicits the cytotoxic activity of iNKT cells and elimination of alpha-GalCer-presenting cells. We report that i.v. injection of alpha-GalCer induced a decrease in the percentage and number of splenic CD8(+)Langerin(+) DCs, while CD8(-) DCs were not affected. The decline in CD8(+) DC numbers was clearly detectable by 15 h after alpha-GalCer injection, was maximal at 24-48 h, returned to normal by day 7, and was accompanied by a reduced cross-presentation of OVA protein given i.v. to specific CD8(+) T cells in vitro. The decrease in the numbers of CD8(+) DCs required iNKT cells but was independent of perforin, Fas, or IFN-gamma, as it was observed in mice deficient in each of these molecules. In contrast, treatment with a TNF-alpha-neutralizing antibody was effective at reducing the decline in CD8(+) DC numbers and DC activation. Treatment with immunostimulatory CpG ODN also resulted in DC activation and a decreased number of CD8(+) DCs; however, the decline in DC number was a result of down-regulation of CD11c and CD8 and did not require iNKT cells or TNF-alpha. Although CD8(+) Langerin(+) DCs appeared to be selectively affected by alpha-GalCer treatment, they were not required for early iNKT cell responses, as their prior depletion did not prevent the increase in serum TNF-alpha and IL-4 observed after alpha-GalCer treatment. Thus, iNKT cells regulate the survival of CD8(+) DCs through a mechanism that does not appear to involve direct cell killing. J. Leukoc. Biol. 89: 753-762; 2011.
Simkins, H. M. A., Hyde, E., Farrand, K. J., Ong, M. L., Degli-Esposti, M., Hermans, I. F., & Ronchese, F. (2011). Administration of alpha-galactosylceramide impairs the survival of dendritic cell subpopulations in vivo. Journal of Leukocyte Biology, 89, 753-762. https://doi.org/10.1189/jlb.0910480