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Updated: May 11, 2026
Artificial Antigen Presenting Cell (aAPC) Mediated Activation and Expansion of Natural Killer T Cells
Published on: December 29, 2012
In-vivo stimulation of macaque natural killer T cells with α-galactosylceramide
C S Fernandez1, S Jegaskanda, D I Godfrey
1Department of Microbiology and Immunology, University of Melbourne, Parkville, Vic., Australia.
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.
Insights
Administering alpha-galactosylceramide (α-GalCer) to macaques depleted natural killer T (NKT) cells and did not enhance anti-viral immunity. This suggests α-GalCer manipulation may not be effective for boosting immunity in non-human primates.
Area of Science:
- Immunology
- Virology
- Primate Research
Background:
- Natural killer T (NKT) cells are crucial for anti-viral immunity in mice.
- Their role and manipulation effects in non-human primates remain largely unknown.
Purpose of the Study:
- To investigate the effects of alpha-galactosylceramide (α-GalCer) administration on NKT cells in macaques.
- To evaluate the impact of α-GalCer on anti-viral immunity in macaque models.
Main Methods:
- 27 macaques received varying doses (1-100 μg) and delivery modes of α-GalCer (intravenous, pulsed onto blood/PBMCs).
- NKT cell populations and cytokine expression were monitored.
- Macaques were subsequently infected with influenza virus or simian immunodeficiency virus (SIV) to assess anti-viral responses.
Main Results:
- Peripheral NKT cells were transiently depleted across all groups, especially at doses ≥10 μg.
- NKT cell numbers remained depressed at intravenous doses >10 μg.
- No significant enhancement of influenza-specific immunity or modulation of SIV infection was observed.
Conclusions:
- α-GalCer administration modulates macaque peripheral NKT cells in vivo.
- The tested dosing regimens did not significantly impact anti-viral immunity in macaque models.
- Further research is needed to explore alternative strategies for NKT cell manipulation in primates.
