生物
免疫学
免疫系统
T细胞
CD8型
T细胞受体
抗原
细胞毒性T细胞
免疫
微生物学
先天免疫系统
获得性免疫系统
受体
作者
Camille Khairallah,Julie A. Bettke,Oleksandr Gorbatsevych,Zhijuan Qiu,Yue Zhang,Kyungjin Cho,Kwang Soon Kim,Timothy H Chu,Jessica Nancy Imperato,Shinya Hatano,Galina Romanov,Yasunobo Yoshikai,Lynn Puddington,Charles D. Surh,James B. Bliska,Adrianus W. M. van der Velden,Brian S. Sheridan
标识
DOI:10.1038/s41385-021-00447-x
摘要
Although murine γδ T cells are largely considered innate immune cells, they have recently been reported to form long-lived memory populations. Much remains unknown about the biology and specificity of memory γδ T cells. Here, we interrogated intestinal memory Vγ4 Vδ1 T cells generated after foodborne Listeria monocytogenes (Lm) infection to uncover an unanticipated complexity in the specificity of these cells. Deep TCR sequencing revealed that a subset of non-canonical Vδ1 clones are selected by Lm infection, consistent with antigen-specific clonal expansion. Ex vivo stimulations and in vivo heterologous challenge infections with diverse pathogenic bacteria revealed that Lm-elicited memory Vγ4 Vδ1 T cells are broadly reactive. The Vγ4 Vδ1 T cell recall response to Lm, Salmonella enterica serovar Typhimurium (STm) and Citrobacter rodentium was largely mediated by the γδTCR as internalizing the γδTCR prevented T cell expansion. Both broadly-reactive canonical and pathogen-selected non-canonical Vδ1 clones contributed to memory responses to Lm and STm. Interestingly, some non-canonical γδ T cell clones selected by Lm infection also responded after STm infection, suggesting some level of cross-reactivity. These findings underscore the promiscuous nature of memory γδ T cells and suggest that pathogen-elicited memory γδ T cells are potential targets for broad-spectrum anti-infective vaccines.
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