Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
J Immunol. 2020 Oct 15;205(8):2169-2187. doi: 10.4049/jimmunol.2000253. Epub 2020 Sep 18.
The choreography of complex immune responses, including the priming, differentiation, and modulation of specific effector T cell populations generated in the immediate wake of an acute pathogen challenge, is in part controlled by chemokines, a large family of mostly secreted molecules involved in chemotaxis and other patho/physiological processes. T cells are both responsive to various chemokine cues and a relevant source for certain chemokines themselves; yet, the actual range, regulation, and role of effector T cell-derived chemokines remains incompletely understood. In this study, using different in vivo mouse models of viral and bacterial infection as well as protective vaccination, we have defined the entire spectrum of chemokines produced by pathogen-specific CD8 and CD4T effector cells and delineated several unique properties pertaining to the temporospatial organization of chemokine expression patterns, synthesis and secretion kinetics, and cooperative regulation. Collectively, our results position the "T cell chemokine response" as a notably prominent, largely invariant, yet distinctive force at the forefront of pathogen-specific effector T cell activities and establish novel practical and conceptual approaches that may serve as a foundation for future investigations into the role of T cell-produced chemokines in infectious and other diseases.
复杂免疫反应的协调,包括在急性病原体挑战后立即产生的特定效应 T 细胞群体的启动、分化和调节,部分受到趋化因子的控制,趋化因子是一个涉及趋化和其他病理/生理过程的大多数分泌分子的大家族。T 细胞既对各种趋化因子线索有反应,又是某些趋化因子的相关来源;然而,效应 T 细胞衍生趋化因子的实际范围、调节和作用仍不完全清楚。在这项研究中,我们使用不同的体内病毒和细菌感染小鼠模型以及保护性疫苗接种,定义了病原体特异性 CD8 和 CD4T 效应细胞产生的所有趋化因子谱,并描绘了与趋化因子表达模式的时空组织、合成和分泌动力学以及协同调节相关的几个独特特性。总的来说,我们的结果将“T 细胞趋化因子反应”定位为病原体特异性效应 T 细胞活动的一个显著、基本不变但独特的力量,并建立了新的实用和概念方法,可为未来研究 T 细胞产生的趋化因子在感染和其他疾病中的作用奠定基础。