Human skin contains a population of memory T cells that supports tissue homeostasis and provides protective immunity. The study of human memory T cells is often restricted to in vitro studies and to human PBMC serving as primary cell source. Because the tissue environment impacts the phenotype and function of memory T cells, it is crucial to study these cells within their tissue. Here we utilized immunodeficient NOD-scid IL2rγ^null (NSG) mice that carried in vivo-generated engineered human skin (ES). ES was generated from human keratinocytes and fibroblasts and was initially devoid of skin-resident immune cells. Upon adoptive transfer of human PBMC, this reductionist system allowed us to study human T cell recruitment from a circulating pool of T cells into non-inflamed human skin in vivo. Circulating human memory T cells preferentially infiltrated ES and showed diverse functional profiles of T cells found in fresh human skin. The chemokine and cytokine microenvironment of ES closely resembled that of non-inflamed human skin. Upon entering the ES T cells assumed a resident memory T cell-like phenotype in the absence of infection, and a proportion of these cutaneous T cells can be locally activated upon injection of monocyte derived dendritic cells (moDCs) that presented Candida albicans. Interestingly, we found that CD69⁺ memory T cells produced higher levels of effector cytokines in response to Candida albicans, compared to CD69^- T cells. Overall, this model has broad utility in many areas of human skin immunology research, including the study of immune-mediated skin diseases.

人体皮肤包含记忆T细胞，这些T细胞支持组织体内稳态并提供保护性免疫。人类记忆T细胞的研究通常仅限于体外研究，而人类PBMC作为主要细胞来源。由于组织环境影响记忆T细胞的表型和功能，因此研究其组织内的这些细胞至关重要。在这里，我们使用免疫缺陷的NOD- SCIDIL2rγ^空，在体内进行（NSG）小鼠-生成的工程人体皮肤（ES）。ES是由人角质形成细胞和成纤维细胞产生的，最初没有皮肤驻留的免疫细胞。在人PBMC的过继转移后，该还原系统使我们能够研究体内T细胞从循环T细胞池进入非发炎的人皮肤的募集。循环中的人类记忆T细胞优先渗透ES，并显示出在新鲜人类皮肤中发现的T细胞的各种功能特征。ES的趋化因子和细胞因子微环境与非发炎的人类皮肤极为相似。进入ES T细胞后，假定其在没有感染的情况下具有常驻记忆T细胞样表型，并且这些皮肤T细胞的一部分可在注射单核细胞衍生的树突状细胞（moDC）后被局部激活白色念珠菌。有趣的是，我们发现与CD69 ^- T细胞相比，CD69 ⁺记忆T细胞对白色念珠菌有更高的效应细胞因子水平。总体而言，该模型在人类皮肤免疫学研究的许多领域具有广泛的用途，包括对免疫介导的皮肤疾病的研究。