Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Mass; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.
Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Mass; Department of Medicine, Harvard Medical School, Boston, Mass.
J Allergy Clin Immunol. 2019 Feb;143(2):565-576.e7. doi: 10.1016/j.jaci.2018.03.022. Epub 2018 May 29.
Infection of suckling mice with influenza virus expands a CD4CD8 double-negative (DN) natural killer T (NKT) cell subpopulation that protects the mice as adults against allergen-induced airway hyperreactivity (AHR). However, this NKT cell subset has not been characterized, and the underlying mechanisms of protection remain unknown.
We characterized this specific NKT cell subpopulation that developed during influenza infection in neonatal mice and that suppressed the subsequent development of AHR.
A cell-surface marker was identified by comparing the mRNA expression profile of wild-type CD4 NKT cells with that of suppressive Vα14 DN NKT cells. The marker-enriched NKT cell subset was then analyzed for its cytokine profile and its suppressive in vitro and in vivo abilities.
We showed that DN NKT cells with high CD38 expression produced IFN-γ, but not IL-17, IL-4, or IL-13, and inhibited development of AHR through contact-dependent suppression of helper CD4 T-cell proliferation. The NKT subset expanded in the lungs of neonatal mice after infection with influenza and also after treatment of neonatal mice with Nu-α-GalCer, which effectively increased DN CD38 NKT cell numbers.
These results suggest that early/neonatal exposure to infection or antigen challenge affects subsequent lung immunity by altering the cellular composition of cells in the lung and that some subsets of NKT cells suppress AHR. These results provide a possible mechanism by which prior infections can protect against the development of allergic asthma and might be further explored as a protective measure for young children.
感染流感病毒会使乳鼠中的 CD4CD8 双阴性（DN）自然杀伤 T（NKT）细胞亚群扩增，该亚群能使成年鼠免受变应原诱导的气道高反应性（AHR）。然而，这种 NKT 细胞亚群尚未被鉴定，其保护机制仍不清楚。
我们对在新生鼠流感感染期间发育并能抑制随后发生的 AHR 的特定 NKT 细胞亚群进行了鉴定。
通过比较野生型 CD4 NKT 细胞与具有抑制作用的 Vα14 DN NKT 细胞的 mRNA 表达谱，确定了一个细胞表面标志物。然后分析了该标志物富集的 NKT 细胞亚群的细胞因子谱及其在体外和体内的抑制能力。
我们发现高表达 CD38 的 DN NKT 细胞产生 IFN-γ，但不产生 IL-17、IL-4 或 IL-13，并通过抑制辅助性 CD4 T 细胞增殖的直接接触抑制作用来抑制 AHR 的发展。流感感染后和用 Nu-α-GalCer 处理新生鼠后，DN CD38 NKT 细胞在肺部扩增，Nu-α-GalCer 能有效增加 DN CD38 NKT 细胞数量。
这些结果表明，早期/新生期感染或抗原刺激会通过改变肺部细胞的组成来影响随后的肺部免疫，而某些 NKT 细胞亚群能抑制 AHR。这些结果提供了一种可能的机制，即先前的感染可以预防过敏性哮喘的发生，并且可能作为一种针对幼儿的保护措施进行进一步研究。
