Jin Niyun, Roark Christina L, Miyahara Nobuaki, Taube Christian, Aydintug M Kemal, Wands J M, Huang Yafei, Hahn Youn-Soo, Gelfand Erwin W, O'Brien Rebecca L, Born Willi K
Integrated Department of Immunology, National Jewish Health, Denver, CO 80206, USA.
J Immunol. 2009 Feb 15;182(4):2002-10. doi: 10.4049/jimmunol.0803280.
Allergic airway hyperresponsiveness (AHR) in OVA-sensitized and challenged mice, mediated by allergen-specific Th2 cells and Th2-like invariant NKT (iNKT) cells, develops under the influence of enhancing and inhibitory gammadelta T cells. The AHR-enhancing cells belong to the Vgamma1(+) gammadelta T cell subset, cells that are capable of increasing IL-5 and IL-13 levels in the airways in a manner like Th2 cells. They also synergize with iNKT cells in mediating AHR. However, unlike Th2 cells, the AHR enhancers arise in untreated mice, and we show here that they exhibit their functional bias already as thymocytes, at an HSA(high) maturational stage. In further contrast to Th2 cells and also unlike iNKT cells, they could not be stimulated to produce IL-4 and IL-13, consistent with their synergistic dependence on iNKT cells in mediating AHR. Mice deficient in IFN-gamma, TNFRp75, or IL-4 did not produce these AHR-enhancing gammadelta T cells, but in the absence of IFN-gamma, spontaneous development of these cells was restored by adoptive transfer of IFN-gamma-competent dendritic cells from untreated donors. The i.p. injection of OVA/aluminum hydroxide restored development of the AHR enhancers in all of the mutant strains, indicating that the enhancers still can be induced when they fail to develop spontaneously, and that they themselves need not express TNFRp75, IFN-gamma, or IL-4 to exert their function. We conclude that both the development and the cytokine potential of the AHR-enhancing gammadelta T cells differs critically from that of Th2 cells and NKT cells, despite similar influences of these cell populations on AHR.
在卵清蛋白（OVA）致敏和激发的小鼠中，变应原特异性Th2细胞和Th2样不变自然杀伤T（iNKT）细胞介导的变应性气道高反应性（AHR）在增强性和抑制性γδT细胞的影响下发展。增强AHR的细胞属于Vγ1(+)γδT细胞亚群，这些细胞能够以类似于Th2细胞的方式增加气道中的白细胞介素-5（IL-5）和白细胞介素-13（IL-13）水平。它们还在介导AHR方面与iNKT细胞协同作用。然而，与Th2细胞不同，AHR增强细胞在未处理的小鼠中出现，并且我们在此表明它们在HSA（高）成熟阶段作为胸腺细胞时就已表现出功能偏向。与Th2细胞以及iNKT细胞进一步不同的是，它们不能被刺激产生IL-4和IL-13，这与其在介导AHR中对iNKT细胞的协同依赖性一致。缺乏干扰素-γ（IFN-γ）、肿瘤坏死因子受体p75（TNFRp75）或IL-4的小鼠不会产生这些增强AHR的γδT细胞，但在缺乏IFN-γ的情况下，通过从未处理供体过继转移具有IFN-γ能力的树突状细胞可恢复这些细胞的自发发育。腹腔注射OVA/氢氧化铝可恢复所有突变株中AHR增强细胞的发育，这表明当增强细胞不能自发发育时仍可被诱导，并且它们自身无需表达TNFRp75、IFN-γ或IL-4来发挥其功能。我们得出结论，尽管这些细胞群体对AHR有相似影响，但增强AHR的γδT细胞的发育和细胞因子潜能与Th2细胞和NKT细胞的发育和细胞因子潜能有很大差异。
