2024年8月29日，《免疫》杂志在线发表了美国匹兹堡大学JoAnne L. Flynn等研究人员的最新合作成果。该研究表明，CD4⁺ T细胞通过重塑肉芽肿细胞组成和调节网络来促进Mtb再感染后的免疫调节。

通过在非人类灵长类动物再感染模型中使用临床和微生物学终点，研究人员证明了先前的结核分枝杆菌（Mtb）感染引发了对随后的Mtb暴露的持久保护性反应，并且这种反应依赖于CD4⁺ T细胞。

通过分析原发感染、再感染和再感染-CD4⁺ T细胞耗竭肉芽肿的数据，研究人员发现再感染期间CD4⁺ T细胞的存在导致了一个炎症较少的肺部环境，这种环境特征为重编程的CD8⁺ T细胞、减少的中性粒细胞增生以及在髓系细胞中的减弱的1型免疫信号。这些结果为开发既针对淋巴细胞又调节先天免疫细胞的疫苗和治疗方法以限制结核病（TB）提供了新的思路。

研究人员表示，免疫学预处理（无论是在先前的感染还是疫苗接种背景下）能够对随后Mtb感染产生保护性反应。然而，原发性Mtb感染后肺部细胞环境发生的变化及其对再感染的保护作用仍然了解不足。

附：英文原文

Title: CD4+ T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection

Author: Joshua D. Bromley, Sharie Keanne C. Ganchua, Sarah K. Nyquist, Pauline Maiello, Michael Chao, H. Jacob Borish, Mark Rodgers, Jaime Tomko, Kara Kracinovsky, Douaa Mugahid, Son Nguyen, Qianchang Dennis Wang, Jacob M. Rosenberg, Edwin C. Klein, Hannah P. Gideon, Roisin Floyd-O’Sullivan, Bonnie Berger, Charles A. Scanga, Philana Ling Lin, Sarah M. Fortune, Alex K. Shalek, JoAnne L. Flynn

Issue&Volume: 2024-08-29

Abstract: Immunological priming—in the context of either prior infection or vaccination—elicits protective responses against subsequent Mycobacterium tuberculosis (Mtb) infection. However, the changes that occur in the lung cellular milieu post-primary Mtb infection and their contributions to protection upon reinfection remain poorly understood. Using clinical and microbiological endpoints in a non-human primate reinfection model, we demonstrated that prior Mtb infection elicited a long-lasting protective response against subsequent Mtb exposure and was CD4+ T cell dependent. By analyzing data from primary infection, reinfection, and reinfection-CD4+ T cell-depleted granulomas, we found that the presence of CD4+ T cells during reinfection resulted in a less inflammatory lung milieu characterized by reprogrammed CD8+ T cells, reduced neutrophilia, and blunted type 1 immune signaling among myeloid cells. These results open avenues for developing vaccines and therapeutics that not only target lymphocytes but also modulate innate immune cells to limit tuberculosis (TB) disease.

DOI: 10.1016/j.immuni.2024.08.002

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00375-3