In‐vivo stimulation of macaque natural killer T cells with α‐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, α‐galactosylceramide (α‐GalCer), in 27 macaques by studying the effects of different dosing (1–100 μg), 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 α‐GalCer administration across all delivery modes, particularly in doses of ≥10 μg. Furthermore, NKT cell numbers frequently remained depressed at i.v. α‐GalCer doses of >10 μg. Levels of cytokine expression were also not enhanced after α‐GalCer delivery to macaques. To evaluate the effects of α‐GalCer administration on anti‐viral immunity, we administered α‐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 α‐GalCer delivery. Further, there was no modulation of pathogenic SIV_mac251 infection following α‐GalCer delivery to a further two macaques in a pilot study. Accordingly, although macaque peripheral NKT cells are modulated by α‐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.