Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI.
Department of Internal Medicine, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI; and.
J Immunol. 2022 Mar 15;208(6):1417-1423. doi: 10.4049/jimmunol.2100819. Epub 2022 Feb 25.
Homotypic signaling lymphocyte activation molecule (SLAM) receptor-ligand cell surface interactions between myeloid and lymphoid cells regulate innate and adaptive immune responses. In this article, we report that SLAMF1 is indispensable for host resistance to primary and vaccine-induced protection against fungal infection. Because vaccine immunity is dependent on cell-mediated immunity, we investigated the development of Ag-specific T cells. We studied the T cell-intrinsic and -extrinsic role of SLAMF1. We generated SLAMF1 TCR transgenic mice and analyzed the responses of adoptively transferred T cells. We also tracked endogenous Ag-specific T cells by using a tetramer. Intrinsic and extrinsic SLAMF1 signaling was dispensable for the development of antifungal Th1 and Th17 cells, which are requisite for the acquisition of vaccine-induced immunity. Despite intact T cell development, vaccinated SLAMF1 mice failed to control fungal infection. Failed accumulation of Ag-specific T cells in the lung on infection of vaccinated mice was due to uncontrolled early infection and inflammation, revealing a role for SLAMF1 in innate host immunity.
同种型信号淋巴细胞激活分子 (SLAM) 受体-配体细胞表面相互作用在髓样细胞和淋巴样细胞之间调节固有和适应性免疫反应。在本文中，我们报告 SLAMF1 对于宿主抵抗原发性和疫苗诱导的真菌感染保护是必不可少的。由于疫苗免疫依赖于细胞介导的免疫，我们研究了 Ag 特异性 T 细胞的发育。我们研究了 SLAMF1 的内在和外在的 T 细胞作用。我们生成了 SLAMF1 TCR 转基因小鼠，并分析了过继转移 T 细胞的反应。我们还通过使用四聚体追踪内源性 Ag 特异性 T 细胞。固有和外在的 SLAMF1 信号对于抗真菌 Th1 和 Th17 细胞的发育是不必要的，而 Th1 和 Th17 细胞是获得疫苗诱导免疫所必需的。尽管 T 细胞发育完整，但接种疫苗的 SLAMF1 小鼠未能控制真菌感染。在接种疫苗的小鼠感染时，Ag 特异性 T 细胞在肺部的积累失控，这是由于早期感染和炎症不受控制，这揭示了 SLAMF1 在先天宿主免疫中的作用。
