Intestinal T cells form a central part of the front‐line defence against foreign organisms and need to be situated in the mucosa where infection occurs. It is well accepted that immunization by a mucosal route favours localization of antigen‐specific effector T cells in the mucosal epithelium, while systemic immunization does not. The aim of the study is to determine how homing receptors are specifically involved in retaining effector T cells in the small intestine after oral immunization. We here demonstrate that the chemokine receptor CXCR6, integrins β7 and CD29 contribute differentially to the epithelial retention phenotype of CD8⁺ T cells in the small intestine of mice. CD8⁺ intraepithelial lymphocytes (IELs) of unvaccinated mice are predominantly β7 single positives, and subcutaneous immunization‐induced antigen‐specific CD8⁺ effector IELs are mainly composed of CXCR6⁺, CD29⁺ and CXCR6⁺CD29⁺ cells. Strikingly, the majority of oral immunization‐induced antigen‐specific CD8⁺ effector IELs exhibit a distinct, tissue‐specific CXCR6⁺β7⁺ double‐positive phenotype, cytotoxic potential and enhanced intraepithelial localization. Transfer of antigen‐specific CD8⁺ T cells preactivated with certain immuno‐stimuli (such as monophosphoryl lipid A) results in increased accumulation of donor IELs with the CXCR6⁺β7⁺ phenotype. As β7 exclusively paired with αE on IELs, our results strongly suggest that CXCR6 may cooperate with the heterodimer αEβ7 to preferentially retain intestinally induced effector IELs in the epithelium. The identification of this novel IEL phenotype has significant implications for the development of vaccines and therapeutic strategies to enhance gut immunity.

中文翻译：

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口服免疫诱导在小肠中占主导地位的新型CXCR6 +β7+上皮内淋巴细胞亚群

肠道T细胞是抵抗外来生物的一线防御的核心部分，需要位于发生感染的粘膜中。众所周知，通过粘膜途径进行的免疫有助于抗原特异性效应T细胞在粘膜上皮中的定位，而全身性免疫则不然。该研究的目的是确定口服免疫后，归巢受体如何特别参与在小肠中保留效应T细胞。我们在这里证明趋化因子受体CXCR6，整合素β7和CD29对小鼠小肠中CD8 ⁺ T细胞的上皮保留表型有不同的贡献。CD8 ⁺未接种疫苗的小鼠的上皮内淋巴细胞（IEL）主要是β7单阳性，皮下免疫诱导的抗原特异性CD8 ⁺效应子IEL主要由CXCR6 ⁺，CD29 ⁺和CXCR6 ⁺ CD29 ⁺细胞组成。令人惊讶的是，大多数口服免疫诱导的抗原特异性CD8 ⁺效应物IEL表现出独特的组织特异性CXCR6 ⁺ β7 ⁺双阳性表型，细胞毒性潜能和增强的上皮内定位。抗原特异性CD8 ^+的转移用某些免疫刺激（例如单磷酰脂质A）预激活的T细胞导致具有CXCR6 ⁺ β7 ⁺表型的供体IEL积累增加。由于β7在IELs上仅与αE配对，因此我们的结果强烈暗示CXCR6可能与异二聚体αEβ7协同作用，在肠上皮中优先保留肠道诱导的效应IELs。这种新的IEL表型的鉴定对疫苗的开发和增强肠道免疫力的治疗策略具有重要意义。