title: In-vivo stimulation of macaque natural killer T cells with α-galactosylceramide.
abstract: 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 SIVmac251 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.
authors: Department of Microbiology and Immunology, University of Melbourne, Parkville, Vic., Australia.
authors: C S
authors: CS
authors: Fernandez
authors: S
authors: S
authors: Jegaskanda
authors: D I
authors: DI
authors: Godfrey
authors: S J
authors: SJ
authors: Kent
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D005699:Galactosylceramides / Q000008:administration & dosage / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D008254:Macaca nemestrina; D008992:Monkey Diseases / Q000276:immunology; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D005699:Galactosylceramides; C493154:alpha-galactosylceramide
keywords: NKT cells; SIV infection; activation; influenza virus; macaques; α-GalCer; α-galactosylceramide
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