HIV and Malaria Vaccine Program, Aaron Diamond AIDS Research Center, Affiliate of the Rockefeller University, New York, NY, USA.
PLoS One. 2012;7(10):e48166. doi: 10.1371/journal.pone.0048166. Epub 2012 Oct 23.
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.
在人类中，不变自然杀伤 T(iNKT)细胞代表外周血单个核细胞(PBMC)中一小部分但具有高度变异性的重要群体。在这项研究中，为了确定适合于临床前糖脂测试的合适非人类灵长类动物模型，我们评估了猪尾猕猴外周血中 iNKT 细胞的百分比和功能。首先，我们使用负载有α-GalCer 的人 CD1d-四聚体(α-GalCer-CD1d-Tet)，发现α-GalCer-CD1d-Tet(+)CD3(+)iNKT 细胞占猪尾猕猴 PBMC 的 0.13%至 0.4%，与人类 PBMC 中 iNKT 细胞的百分比相当。其次，我们观察到很大比例的 Vα24(+)CD3(+)细胞是α-GalCer-CD1d-Tet(+)CD3(+)iNKT 细胞，主要由 CD4(+)或 CD8(+)亚群组成。第三，我们发现猪尾猕猴 iNKT 细胞在α-GalCer 的刺激下产生 IFN-γ，如 ELISpot 测定和细胞内细胞因子染色(ICCS)所示，以及 TNF-α，如 ICCS 所示，表明这些 iNKT 细胞具有完全功能。有趣的是，大多数分泌 IFN-γ的猪尾猕猴 iNKT 细胞是 CD8(+)iNKT 细胞。基于这些发现，我们得出结论，猪尾猕猴具有作为临床前刺激 iNKT 糖脂测试的非人类动物模型的潜力。
