Abstract
In humans, invariant natural killer T (iNKT) cells represent a small but significant population of peripheral blood mononuclear cells (PBMCs) with a high degree of variability. In this study, pursuant to our goal of identifying an appropriate non-human primate model suitable for pre-clinical glycolipid testing, we evaluated the percentage and function of iNKT cells in the peripheral blood of pig-tailed macaques. First, using a human CD1d-tetramer loaded with α-GalCer (α-GalCer-CD1d-Tet), we found that α-GalCer-CD1d-Tet+ CD3+ iNKT cells make up 0.13% to 0.4% of pig-tailed macaque PBMCs, which are comparable to the percentage of iNKT cells found in human PBMCs. Second, we observed that a large proportion of Vα24+CD3+ cells are α-GalCer-CD1d-Tet+CD3+ iNKT cells, which primarily consist of either the CD4+ or CD8+ subpopulation. Third, we found that pig-tailed macaque iNKT cells produce IFN-γ in response to α-GalCer, as shown by ELISpot assay and intracellular cytokine staining (ICCS), as well as TNF-α, as shown by ICCS, indicating that these iNKT cells are fully functional. Interestingly, the majority of pig-tailed macaque iNKT cells that secrete IFN-γ are CD8+ iNKT cells. Based on these findings, we conclude that the pig-tailed macaques exhibit potential as a non-human animal model for the pre-clinical testing of iNKT-stimulating glycolipids.
Highlights
Natural killer T (NKT) cells are a unique subset of lymphoid cells that express both a T cell antigen receptor (TCR) and NK1.1 (NKR-P1 or CD161c), a C-lectin-type NK receptor [1,2]
Upon stimulation, invariant NKT (iNKT) cells, like NK cells, display cytotoxic activity mediated by Fas, perforin, granzyme A/B, and granulysin [13,14]. iNKT cells have been shown to display anti-tumor activity [15,16], mediate therapeutic effects against autoimmune diseases [17,18,19,20], and promote protection against certain infectious agents [21,22,23,24]
We aimed to characterize the properties of iNKT cells derived from pig-tailed macaques to determine whether the cells in this species exhibit similar properties to human iNKT cells
Summary
Natural killer T (NKT) cells are a unique subset of lymphoid cells that express both a T cell antigen receptor (TCR) and NK1.1 (NKR-P1 or CD161c), a C-lectin-type NK receptor [1,2]. Some studies have investigated the frequency, phenotype, and function of iNKT cells derived from non-human primates, including pig-tailed macaques, and found similar percentages and high variability of iNKT cells between monkeys and humans [27,28,29,30]. These studies have indicated that the phenotypes and functions of monkey iNKT cells are significantly different among different macaque species [27,28,29,30].
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