In-vivo stimulation of macaque natural killer T cells with -galactosylceramide

Natural killer T cells are a potent mediator of anti-viral immunity in mice, but little is known about the effects of manipulating NKT cells in non-human primates. We evaluated the delivery of the NKT cell ligand, -galactosylceramide (-GalCer), in 27 macaques by studying the effects of different dosing (1-100g), and delivery modes [directly intravenously (i.v.) or pulsed onto blood or peripheral blood mononuclear cells]. We found that peripheral NKT cells were depleted transiently from the periphery following -GalCer administration across all delivery modes, particularly in doses of 10g. Furthermore, NKT cell numbers frequently remained depressed at i.v. -GalCer doses of >10g. Levels of cytokine expression were also not enhanced after -GalCer delivery to macaques. To evaluate the effects of -GalCer administration on anti-viral immunity, we administered -GalCer either together with live attenuated influenza virus infection or prior to simian immunodeficiency virus (SIV) infection of two macaques. There was no clear enhancement of influenza-specific T or B cell immunity following -GalCer delivery. Further, there was no modulation of pathogenic SIVmac251 infection following -GalCer delivery to a further two macaques in a pilot study. Accordingly, although macaque peripheral NKT cells are modulated by -GalCer in vivo, at least for the dosing regimens tested in this study, this does not appear to have a significant impact on anti-viral immunity in macaque models.