CD4+ T cell immunity to Salmonella is transient in the circulation.
CD4+ T cell immunity to Salmonella is transient in the circulation.
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DOI：
10.1371/journal.ppat.1010004
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发表时间：
2021-10
期刊：
影响因子：
6.7
通讯作者：
Strugnell RA
中科院分区：
文献类型：
--
作者：
Peres NG;Wang N;Whitney P;Engel S;Shreenivas MM;Comerford I;Hocking DM;Erazo AB;Förster I;Kupz A;Gebhardt T;McColl SR;McSorley SJ;Bedoui S;Strugnell RA
虽然肠沙门氏菌被视为一种典型的兼性细胞内细菌病原体，其保护作用是由 CD4+ T 细胞介导的，但事实证明，识别循环保护细胞非常困难，从而抑制了识别关键抗原特异性的步骤。利用小鼠疫苗接种模型，我们发现，接种减毒活鼠伤寒沙门氏菌（S.Typhimurium）菌株的 C57BL/6 小鼠的脾脏携带大量 IFN-γ+ CD4+ T 细胞，这些细胞可以过继性转移保护，但只是短暂的。循环沙门氏菌反应性 CD4+ T 细胞表达肝脏归巢趋化因子受体 CXCR6，随着时间的推移在肝脏中积累，并呈现与组织相关 T 细胞相关的表型特征。肝脏记忆 CD4+ T 细胞表现出 TCR 选择偏差，并且可以通过阻断 CXCL16 来抑制它们在肝脏中的积累。这些数据表明，介导沙门氏菌免疫的 CD4+ T 细胞的循环仅限于一个短暂的窗口，此后沙门氏菌特异性 CD4+ T 细胞迁移到外周组织。我们的观察强调了引发针对全身感染的组织特异性免疫的重要性。辅助 T 细胞对于控制细菌病原体（例如鼠伤寒沙门氏菌（S. Typhimurium））的感染至关重要。虽然已明确这一作用与其提供 IFN-γ 有关，但辅助 T 细胞何时何地在体内引发其保护功能仍悬而未决。我们在接种生长减毒的鼠伤寒沙门氏菌菌株后不久，就在小鼠循环中发现了保护性辅助 T 细胞群；随着时间的推移，这个人口逐渐减少。我们观察到，当从短时间窗口收获时，循环辅助 T 细胞免疫可以过继地保护幼稚受体小鼠免受致命的鼠伤寒沙门氏菌感染。在比较沙门氏菌感染小鼠的脾脏和肝脏之间的辅助 T 细胞反应时，我们观察到辅助 T 细胞向肝脏的先前未表征的运输，随后鼠伤寒沙门氏菌特异性 T 细胞记忆在该器官中驻留。综上所述，这些发现表明，对沙门氏菌感染的保护性免疫在循环系统和肝脏中是短暂的，而肝脏是辅助性 T 记忆细胞的优先部位。
While Salmonella enterica is seen as an archetypal facultative intracellular bacterial pathogen where protection is mediated by CD4+ T cells, identifying circulating protective cells has proved very difficult, inhibiting steps to identify key antigen specificities. Exploiting a mouse model of vaccination, we show that the spleens of C57BL/6 mice vaccinated with live-attenuated Salmonella serovar Typhimurium (S. Typhimurium) strains carried a pool of IFN-γ+ CD4+ T cells that could adoptively transfer protection, but only transiently. Circulating Salmonella-reactive CD4+ T cells expressed the liver-homing chemokine receptor CXCR6, accumulated over time in the liver and assumed phenotypic characteristics associated with tissue-associated T cells. Liver memory CD4+ T cells showed TCR selection bias and their accumulation in the liver could be inhibited by blocking CXCL16. These data showed that the circulation of CD4+ T cells mediating immunity to Salmonella is limited to a brief window after which Salmonella-specific CD4+ T cells migrate to peripheral tissues. Our observations highlight the importance of triggering tissue-specific immunity against systemic infections. Helper T cells are essential for controlling infections by bacterial pathogens, such as Salmonella enterica var Typhimurium (S. Typhimurium). While it is well-established that this role is related to their provision of IFN-γ, when and where helper T cells elicit their protective function in vivo remains unresolved. We identified a protective helper T cell population in the circulation of mice early after inoculation with growth-attenuated S. Typhimurium strains; this population waned overtime. We observed that circulating helper T cell immunity can adoptively protect naïve recipient mice against lethal S. Typhimurium infection when harvested from a short time-window. In comparing helper T cell responses between spleen and liver in Salmonella-infected mice, we have observed a previously uncharacterized trafficking of helper T cells to the liver followed by the residence of S. Typhimurium-specific T cell memory in the organ. Taken together these findings identify that protective immunity to Salmonella infections is transient in the circulation and the liver as a preferential site of helper T memory cells.
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趋化因子受体CXCR3促进CD8（+）T细胞分化为短寿命的效应细胞，导致记忆变性。
DOI：
10.1084/jem.20102101
发表时间：
2011-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kurachi M;Kurachi J;Suenaga F;Tsukui T;Abe J;Ueha S;Tomura M;Sugihara K;Takamura S;Kakimi K;Matsushima K
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32.4
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Jenkins, MK
DOI：
10.1073/pnas.96.18.10338
发表时间：
1999-08-31
影响因子：
11.1
作者：
Madsen, L;Labrecque, N;Fugger, L
通讯作者：
Fugger, L
影响因子：
4.4
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通讯作者：
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影响因子：
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