Thierry A, Robin A, Giraud S, Minouflet S, Barra A, Bridoux F, Hauet T, Touchard G, Herbelin A, Gombert J-M
Department of Nephrology and Transplantation, CHU of Poitiers, 86021 Poitiers, France.
Vet Immunol Immunopathol. 2012 Oct 15;149(3-4):272-9. doi: 10.1016/j.vetimm.2012.06.023. Epub 2012 Jul 4.
The pig is a relevant preclinical model for numerous pathologies used to validate therapeutic strategies for translation to human. Although invariant natural killer T (iNKT) lymphocytes are a component of innate immunity implicated in many pathological processes, little is known on their characterization in swine. By addressing this issue using mouse α-galactosylceramide-loaded CD1d tetramers (α-GC-CD1dTT), which are commonly used to track iNKT cells, we were able to unequivocally identify CD3(+)α-GC-CD1dTT(+) cells in porcine peripheral blood, hereafter referred to as swine iNKT cells. These lymphocytes are enriched in CD4(-)CD8(+) and CD4(-)CD8(-) cells, harbor an activated-memory phenotype (SLA-DR(+)CD45RA(-)), express the intracellular promyelocytic-leukemia-zinc-finger (PLZF) transcription factor and are significantly enriched in IFN-γ-producing cells after in vitro activation in comparison with conventional T cells. Importantly, in presence of IL-2 and IL-15, the iNKT cell ligand α-GC induces selective expansion of CD3(+)α-GC-CD1dTT(+) cells, confirming the reactivity of swine iNKT cells against α-GC. When associated with α-GC, IL-33, an alarmin of IL-1 family recently described to target iNKT cells, leads to a greater expansion of CD3(+)α-GC-CD1dTT(+) cells than IL-2 and IL-15. Altogether, our results provide the first phenotypic and functional description of swine iNKT cells allowing to further study the critical role of iNKT cells in porcine models of organ injury.
猪是用于验证向人类转化的治疗策略的多种病理的相关临床前模型。尽管不变自然杀伤T（iNKT）淋巴细胞是参与许多病理过程的固有免疫的一个组成部分，但关于它们在猪中的特征知之甚少。通过使用常用于追踪iNKT细胞的小鼠α-半乳糖神经酰胺负载的CD1d四聚体（α-GC-CD1dTT）来解决这个问题，我们能够明确鉴定猪外周血中的CD3(+)α-GC-CD1dTT(+)细胞，以下称为猪iNKT细胞。这些淋巴细胞在CD4(-)CD8(+)和CD4(-)CD8(-)细胞中富集，具有活化记忆表型（SLA-DR(+)CD45RA(-)），表达细胞内早幼粒细胞白血病锌指（PLZF）转录因子，并且与传统T细胞相比，在体外活化后产生IFN-γ的细胞中显著富集。重要的是，在IL-2和IL-15存在的情况下，iNKT细胞配体α-GC诱导CD3(+)α-GC-CD1dTT(+)细胞的选择性扩增，证实了猪iNKT细胞对α-GC的反应性。当与α-GC相关联时，IL-33是最近描述的靶向iNKT细胞的IL-1家族警报素，它比IL-2和IL-15导致更大的CD3(+)α-GC-CD1dTT(+)细胞扩增。总之，我们的结果提供了猪iNKT细胞的首次表型和功能描述，从而能够进一步研究iNKT细胞在猪器官损伤模型中的关键作用。
