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CD4 T cell help prevents CD8 T cell exhaustion and promotes control of Mycobacterium tuberculosis infection
Cell Reports ( IF 8.8 ) Pub Date : 2021-09-14 , DOI: 10.1016/j.celrep.2021.109696
Yu-Jung Lu 1 , Palmira Barreira-Silva 2 , Shayla Boyce 3 , Jennifer Powers 3 , Kelly Cavallo 3 , Samuel M Behar 1
Affiliation  

CD4 T cells are essential for immunity to tuberculosis because they produce cytokines, including interferon-γ. Whether CD4 T cells act as “helper” cells to promote optimal CD8 T cell responses during Mycobacterium tuberculosis is unknown. Using two independent models, we show that CD4 T cell help enhances CD8 effector functions and prevents CD8 T cell exhaustion. We demonstrate synergy between CD4 and CD8 T cells in promoting the survival of infected mice. Purified helped, but not helpless, CD8 T cells efficiently restrict intracellular bacterial growth in vitro. Thus, CD4 T cell help plays an essential role in generating protective CD8 T cell responses against M. tuberculosis infection in vitro and in vivo. We infer vaccines that elicit both CD4 and CD8 T cells are more likely to be successful than vaccines that elicit only CD4 or CD8 T cells.



中文翻译:

CD4 T 细胞有助于防止 CD8 T 细胞衰竭并促进控制结核分枝杆菌感染

CD4 T 细胞对结核病免疫至关重要,因为它们产生细胞因子,包括干扰素-γ。CD4 T 细胞是否充当“辅助”细胞以促进结核分枝杆菌期间的最佳 CD8 T 细胞反应尚不清楚。使用两个独立的模型,我们表明 CD4 T 细胞有助于增强 CD8 效应器功能并防止 CD8 T 细胞衰竭。我们展示了 CD4 和 CD8 T 细胞在促进受感染小鼠存活方面的协同作用。纯化的 CD8 T 细胞有助于但并非无助于体外有效限制细胞内细菌的生长。因此,CD4 T 细胞帮助在体外体内产生针对结核分枝杆菌感染的保护性 CD8 T 细胞反应中发挥重要作用. 我们推断同时引发 CD4 和 CD8 T 细胞的疫苗比仅引发 CD4 或 CD8 T 细胞的疫苗更有可能成功。

更新日期:2021-09-15
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