近日，美国华盛顿大学Chetan Seshadri等研究人员合作发现，特定CD4⁺ T细胞表型与“抵抗”结核分枝杆菌感染者的细菌控制有关。相关论文于2024年7月12日在线发表在《自然—免疫学》杂志上。

研究人员表示，一部分暴露于结核分枝杆菌（Mtb）的人群被称为“抵抗者”（RSTR），尽管临床测试结果连续为阴性，但显示出对Mtb特异性抗原的IFN-γ⁻ T细胞反应。

研究人员发现，RSTR中的Mtb特异性T细胞呈克隆性扩展，证实了在Mtb暴露后适应性免疫反应的启动。与具有潜伏性Mtb感染的个体相比，RSTR CD4⁺ T细胞显示出T_H17和调节性T细胞样功能程序的富集。

利用公共数据集，研究人员表明这些T_H17细胞样功能程序与南非青少年潜伏性Mtb感染中缺乏进展为活动性结核病以及在非人灵长类中对细菌的控制相关。

研究结果表明，RSTR在暴露和免疫启动后可能成功控制Mtb，并建立了一套T细胞生物标志物以促进对这种临床表型的进一步研究。

附：英文原文

Title: Specific CD4+ T cell phenotypes associate with bacterial control in people who ‘resist’ infection with Mycobacterium tuberculosis

Author: Sun, Meng, Phan, Jolie M., Kieswetter, Nathan S., Huang, Huang, Yu, Krystle K. Q., Smith, Malisa T., Liu, Yiran E., Wang, Chuanqi, Gupta, Sanjana, Obermoser, Gerlinde, Maecker, Holden Terry, Krishnan, Akshaya, Suresh, Sundari, Gupta, Neha, Rieck, Mary, Acs, Peter, Ghanizada, Mustafa, Chiou, Shin-Heng, Khatri, Purvesh, Boom, W. Henry, Hawn, Thomas R., Stein, Catherine M., Mayanja-Kizza, Harriet, Davis, Mark M., Seshadri, Chetan

Issue&Volume: 2024-07-12

Abstract: A subset of individuals exposed to Mycobacterium tuberculosis (Mtb) that we refer to as ‘resisters’ (RSTR) show evidence of IFN-γ T cell responses to Mtb-specific antigens despite serially negative results on clinical testing. Here we found that Mtb-specific T cells in RSTR were clonally expanded, confirming the priming of adaptive immune responses following Mtb exposure. RSTR CD4+ T cells showed enrichment of TH17 and regulatory T cell-like functional programs compared to Mtb-specific T cells from individuals with latent Mtb infection. Using public datasets, we showed that these TH17 cell-like functional programs were associated with lack of progression to active tuberculosis among South African adolescents with latent Mtb infection and with bacterial control in nonhuman primates. Our findings suggested that RSTR may successfully control Mtb following exposure and immune priming and established a set of T cell biomarkers to facilitate further study of this clinical phenotype.

DOI: 10.1038/s41590-024-01897-8

Source: https://www.nature.com/articles/s41590-024-01897-8