Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
J Immunol. 2010 Aug 15;185(4):2157-63. doi: 10.4049/jimmunol.1000359. Epub 2010 Jul 16.
Invariant NKT (iNKT) cells were shown to prevent the onset of experimental autoimmune encephalomyelitis in mice following administration of their specific TCR agonist alpha-galactosylceramide. We found that this protection was associated with the emergence of a Foxp3(+) iNKT cell population in cervical lymph nodes. We demonstrate that the differentiation of these cells is critically dependent on TGF-beta in both mice and humans. Moreover, in vivo generation of Foxp3(+) iNKT cells was observed in the TGF-beta-rich environment of the murine gut. Foxp3(+) iNKT cells displayed a phenotype similar to that of Foxp3(+) regulatory T cells, and they suppress through a contact-dependent, glucocorticoid-induced TNFR-mediated mechanism. Nevertheless, Foxp3(+) iNKT cells retain distinctive NKT cell characteristics, such as promyelocytic leukemia zinc finger protein expression and preferential homing to the liver following adoptive transfer, where they stably maintained Foxp3 expression. Our data thus unveil an unexpected capacity of iNKT cells to acquire regulatory functions that may contribute to the establishment of immunological tolerance.
不变自然杀伤 T(iNKT)细胞被证明可在给予其特异性 T 细胞受体激动剂半乳糖神经酰胺后预防实验性自身免疫性脑脊髓炎在小鼠中的发生。我们发现这种保护与颈淋巴结中出现 Foxp3(+)iNKT 细胞群体有关。我们证明，这些细胞的分化在小鼠和人类中都严重依赖 TGF-β。此外，在富含 TGF-β的小鼠肠道环境中观察到体内生成 Foxp3(+)iNKT 细胞。Foxp3(+)iNKT 细胞表现出与 Foxp3(+)调节性 T 细胞相似的表型，通过依赖接触、糖皮质激素诱导的 TNFR 介导的机制进行抑制。然而，Foxp3(+)iNKT 细胞保留独特的 iNKT 细胞特征，如早幼粒细胞白血病锌指蛋白表达，并在过继转移后优先归巢到肝脏，在那里它们稳定地维持 Foxp3 表达。因此，我们的数据揭示了 iNKT 细胞获得调节功能的意外能力，这可能有助于建立免疫耐受。
