A blend of broadly-reactive and pathogen-selected Vγ4 Vδ1 T cell receptors confer broad bacterial reactivity of resident memory γδ T cells.
A blend of broadly-reactive and pathogen-selected Vγ4 Vδ1 T cell receptors confer broad bacterial reactivity of resident memory γδ T cells.
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广泛反应和病原体选择的Vγ4Vδ1T细胞受体的混合物赋予了居民记忆γδT细胞的广泛细菌反应性。
DOI：
10.1038/s41385-021-00447-x
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发表时间：
2022-01
影响因子：
8
通讯作者：
Sheridan BS
中科院分区：
文献类型：
--
作者：
Khairallah C;Bettke JA;Gorbatsevych O;Qiu Z;Zhang Y;Cho K;Kim KS;Chu TH;Imperato JN;Hatano S;Romanov G;Yoshikai Y;Puddington L;Surh CD;Bliska JB;van der Velden AWM;Sheridan BS
虽然小鼠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形成了长寿的记忆群体。记忆γδ T细胞的生物学和特异性仍有许多未知之处。在这里，我们研究了食源性单核增生李斯特菌（Listeria monocytogenes, Lm）感染后产生的肠道记忆Vγ4Vδ1 T细胞，以揭示这些细胞特异性的意想不到的复杂性。深TCR测序显示，Lm感染选择了一个非典型Vδ1克隆亚群，与抗原特异性克隆扩增一致。体外刺激和体内不同致病菌的异体攻击感染表明，lm诱导的记忆Vγ4Vδ1 T细胞具有广泛的反应性。γδTCR内化抑制了T细胞的扩增，从而在很大程度上介导了v - γ - 4v δ1 T细胞对Lm、肠炎沙门氏菌血清型鼠伤寒杆菌（STm）和鼠柠檬酸杆菌的召回反应。广泛反应的典型和病原体选择的非典型Vδ1克隆都有助于对Lm和STm的记忆反应。有趣的是，Lm感染选择的一些非典型γδ T细胞克隆在STm感染后也有应答，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，并提示病原体引发的记忆γδ T细胞是广谱抗感染疫苗的潜在靶标。
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 Vγ4Vδ1 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 Vγ4Vδ1 T cells are broadly reactive. The Vγ4Vδ1 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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影响因子：
16.6
作者：
Davey MS;Willcox CR;Hunter S;Kasatskaya SA;Remmerswaal EBM;Salim M;Mohammed F;Bemelman FJ;Chudakov DM;Oo YH;Willcox BE
通讯作者：
Willcox BE
影响因子：
4.4
作者：
Misiak, Alicja;Wilk, Mieszko M.;Mills, Kingston H. G.
通讯作者：
Mills, Kingston H. G.
影响因子：
4.4
作者：
Murphy, Alison G.;O'Keeffe, Kate M.;McLoughlin, Rachel M.
通讯作者：
McLoughlin, Rachel M.
影响因子：
5.4
作者：
Koenecke, Christian;Chennupati, Vijaykumar;Prinz, Immo
通讯作者：
Prinz, Immo
影响因子：
16.8
作者：
Chien YH;Zeng X;Prinz I
通讯作者：
Prinz I