Our understanding of tissue-resident memory T (T RM ) cell biology has been largely developed from acute infection models in which antigen is cleared and sterilizing immunity is achieved. Less is known about T RM cells in the context of chronic antigen persistence and inflammation. We investigated factors that underlie T RM maintenance in a kidney transplantation model in which T RM cells drive rejection. In contrast to acute infection, we found that T RM cells declined markedly in the absence of cognate antigen, antigen presentation, or antigen sensing by the T cells. Depletion of graft-infiltrating dendritic cells or interruption of antigen presentation after T RM cells were established was sufficient to disrupt T RM maintenance and reduce allograft pathology. Likewise, removal of IL-15 transpresentation or of the IL-15 receptor on T cells during T RM maintenance led to a decline in T RM cells, and IL-15 receptor blockade prevented chronic rejection. Therefore, antigen and IL-15 presented by dendritic cells play nonredundant key roles in CD8 T RM cell maintenance in settings of antigen persistence and inflammation. These findings provide insights that could lead to improved treatment of chronic transplant rejection and autoimmunity.

中文翻译：

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抗原持续期间组织驻留记忆 T 细胞的维持需要同源抗原和白细胞介素 15

我们对组织驻留记忆 T (TR M）细胞生物学很大程度上是从急性感染模型发展而来的，其中抗原被清除并实现了灭菌免疫。对T知之甚少R M慢性抗原持续存在和炎症背景下的细胞。我们调查了 T 背后的因素R M肾移植模型中的维持，其中 TR M细胞驱动排斥反应。与急性感染相反，我们发现TR M在缺乏同源抗原、抗原呈递或 T 细胞抗原感应的情况下，细胞数量显着下降。T 后移植物浸润树突状细胞的消耗或抗原呈递的中断R M细胞的建立足以破坏T细胞R M维护并减少同种异体移植物的病理。同样，T细胞上的IL-15转呈或IL-15受体的去除R M维护导致 T 下降R M细胞和 IL-15 受体阻断可防止慢性排斥反应。因此，树突状细胞呈递的抗原和IL-15在CD8 T中发挥着非冗余的关键作用。R M抗原持续存在和炎症环境下的细胞维持。这些发现提供了一些见解，可以改善慢性移植排斥和自身免疫的治疗。