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.

尽管小鼠 γδ T 细胞在很大程度上被认为是先天免疫细胞，但最近有报道称它们可以形成长寿记忆细胞群。关于记忆 γδ T 细胞的生物学和特异性还有很多未知。在这里，我们研究了食源性单核细胞增生李斯特菌( Lm ) 感染后产生的肠道记忆 Vγ4 Vδ1 T 细胞，以揭示这些细胞特异性中意想不到的复杂性。深度 TCR 测序表明， Lm感染选择了一个非经典 Vδ1 克隆子集，这与抗原特异性克隆扩增一致。体外刺激和体内异源挑战感染多种病原菌表明Lm-诱发的记忆 Vγ4 Vδ1 T 细胞具有广泛的反应性。Vγ4 Vδ1 T 细胞对Lm、鼠伤寒沙门氏菌 ( S Tm) 和柠檬酸杆菌的召回反应主要由 γδTCR 介导，因为内化 γδTCR 会阻止 T 细胞扩增。广泛反应性规范和病原体选择的非规范 Vδ1 克隆都有助于对Lm和S Tm 的记忆反应。有趣的是，一些通过Lm感染选择的非经典 γδ T 细胞克隆在S后也有反应Tm 感染，表明存在一定程度的交叉反应。这些发现强调了记忆 γδ T 细胞的混杂性质，并表明病原体引发的记忆 γδ T 细胞是广谱抗感染疫苗的潜在靶标。