美国匹兹堡大学Timothy W. Hand研究组发现，环境性肠道功能紊乱诱导调节性T细胞，从而抑制局部CD4⁺T细胞反应并损害口服疫苗的功效。这一研究成果于2021年8月3日在线发表在国际学术期刊《免疫》上。

为了研究环境性肠功能紊乱（EED）期间口服疫苗失败的机制，研究人员建立了一个微生物群和饮食依赖的小鼠EED模型。对这些小鼠的大肠杆菌毒素疫苗特异性CD4⁺T细胞的分析显示，小肠的CD4⁺T细胞反应受损，但淋巴结的却没有。EED小鼠表现出小肠驻留的RORγT⁺FOXP3⁺调节性T（Treg）细胞的频率增加。从Treg细胞中靶向删除RORγT可恢复小肠疫苗特异性的CD4 T细胞反应和疫苗介导的感染保护。然而，RORγT⁺FOXP3⁺Treg细胞的缺乏使小鼠更容易受到EED引起的发育不良的影响。这些研究结果提供了对口服疫苗在EED中疗效不佳的见解，并强调了RORγT⁺FOXP3⁺Treg细胞如何能调节肠道免疫，同时使全身反应保持完整。

据悉，EED是一种由营养不良和慢性感染引起的胃肠道炎症性疾病。EED与儿童的发育不良和口服疫苗的效力降低有关。

附：英文原文

Title: Environmental enteric dysfunction induces regulatory T cells that inhibit local CD4+ T cell responses and impair oral vaccine efficacy

Author: Amrita Bhattacharjee, Ansen H.P. Burr, Abigail E. Overacre-Delgoffe, Justin T. Tometich, Deyi Yang, Brydie R. Huckestein, Jonathan L. Linehan, Sean P. Spencer, Jason A. Hall, Oliver J. Harrison, Denise Morais da Fonseca, Elizabeth B. Norton, Yasmine Belkaid, Timothy W. Hand

Issue&Volume: 2021-08-03

Abstract: Environmental enteric dysfunction (EED) is a gastrointestinal inflammatory diseasecaused by malnutrition and chronic infection. EED is associated with stunting in childrenand reduced efficacy of oral vaccines. To study the mechanisms of oral vaccine failureduring EED, we developed a microbiota- and diet-dependent mouse EED model. Analysisof E. coli-labile toxin vaccine-specific CD4+ T cells in these mice revealed impaired CD4+ T cell responses in the small intestine and but not the lymph nodes. EED mice exhibitedincreased frequencies of small intestine-resident RORγT+FOXP3+ regulatory T (Treg) cells. Targeted deletion of RORγT from Treg cells restored smallintestinal vaccine-specific CD4 T cell responses and vaccine-mediated protection uponchallenge. However, ablation of RORγT+FOXP3+ Treg cells made mice more susceptible to EED-induced stunting. Our findings provideinsight into the poor efficacy of oral vaccines in EED and highlight how RORγT+FOXP3+ Treg cells can regulate intestinal immunity while leaving systemic responses intact.

DOI: 10.1016/j.immuni.2021.07.005

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00291-0