Memory T cells possess an innate-like function in local protection from mucosal infection.
Memory T cells possess an innate-like function in local protection from mucosal infection.
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DOI：
10.1172/jci162800
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发表时间：
2023-05-15
影响因子：
15.9
通讯作者：
Lund, Jennifer M.
中科院分区：
文献类型：
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作者：
Arkatkar, Tanvi;Dave, Veronica;Talavera, Irene Cruz;Graham, Jessica B.;Swarts, Jessica L.;Hughes, Sean M.;Bell, Timothy A.;Hock, Pablo;Farrington, Joe;Shaw, Ginger D.;Kirby, Anna;Fialkow, Michael;Huang, Meei-Li;Jerome, Keith R.;Ferris, Martin T.;Hladik, Florian;Schiffer, Joshua T.;Prlic, Martin;Lund, Jennifer M.
粘液菌感染造成了严重的全球健康负担。抗原特异性组织驻留T细胞对维持屏障免疫至关重要。先前在全身感染背景下的研究表明，记忆性CD 8 + T细胞也可能提供对抗原无关病原体的先天性保护，而不依赖于T细胞受体的参与。旁观者T细胞活化是否也是粘膜中的重要防御机制尚不清楚。在这里，我们研究了先天性记忆性CD 8 + T细胞是否可以防止模型粘膜病毒感染，单纯疱疹病毒2（HSV-2）。我们发现，用不相关抗原免疫延迟了致命HSV-2攻击的疾病进展，这表明尽管缺乏抗原特异性，但记忆性CD 8 + T细胞可能介导保护作用。在HSV-2感染后，我们观察到抗原非特异性CD 8 + T细胞的早期浸润，而不是大量的局部增殖，这些细胞仅在感染的粘膜组织内被旁观者激活。重要的是，我们表明，旁观者激活的CD 8 + T细胞足以减少HSV-2感染后的早期病毒负荷。最后，感染后组织微环境内的局部细胞因子线索足以使来自小鼠和人的粘膜组织记忆性CD 8 + T细胞的旁观者活化。总之，我们的研究结果表明，局部旁观者激活的CD 8+记忆T细胞有助于快速和有效的先天性样反应，感染粘膜组织。
Mucosal infections pose a significant global health burden. Antigen-specific tissue-resident T cells are critical to maintaining barrier immunity. Previous studies in the context of systemic infection suggest that memory CD8+ T cells may also provide innate-like protection against antigenically unrelated pathogens independent of T cell receptor engagement. Whether bystander T cell activation is also an important defense mechanism in the mucosa is poorly understood. Here, we investigated whether innate-like memory CD8+ T cells could protect against a model mucosal virus infection, herpes simplex virus 2 (HSV-2). We found that immunization with an irrelevant antigen delayed disease progression from lethal HSV-2 challenge, suggesting that memory CD8+ T cells may mediate protection despite the lack of antigen specificity. Upon HSV-2 infection, we observed an early infiltration, rather than substantial local proliferation, of antigen-nonspecific CD8+ T cells, which became bystander-activated only within the infected mucosal tissue. Critically, we show that bystander-activated CD8+ T cells are sufficient to reduce early viral burden after HSV-2 infection. Finally, local cytokine cues within the tissue microenvironment after infection were sufficient for bystander activation of mucosal tissue memory CD8+ T cells from mice and humans. Altogether, our findings suggest that local bystander activation of CD8+ memory T cells contributes a fast and effective innate-like response to infection in mucosal tissue.