Mucosal Immunol. 2021 Aug 30; doi: 10.1038/s41385-021-00447-x. Epub 2021 Aug 30.

A blend of broadly-reactive and pathogen-selected Vγ4 Vδ1 T cell receptors confer broad bacterial reactivity of resident memory γδ T cells.

Mucosal immunology

Camille Khairallah, Julie A Bettke, Oleksandr Gorbatsevych, Zhijuan Qiu, Yue Zhang, Kyungjin Cho, Kwang Soon Kim, Timothy H Chu, Jessica N Imperato, Shinya Hatano, Galina Romanov, Yasunobo Yoshikai, Lynn Puddington, Charles D Surh, James B Bliska, Adrianus W M van der Velden, Brian S Sheridan

PMID: 34462572 DOI: 10.1038/s41385-021-00447-x

Abstract

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.

© 2021. The Author(s), under exclusive licence to Society for Mucosal Immunology.

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Publication Types

• Journal Article

Grant support

• K12 GM102778/GM/NIGMS NIH HHS/United States
• R21 AG058981/AG/NIA NIH HHS/United States