Nolz Jeffrey C
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, 6516 Richard Jones Hall, 3181 SW Sam Jackson Park Road, Mail Code: L220, Portland, OR, 97239, USA,
Cell Mol Life Sci. 2015 Jul;72(13):2461-73. doi: 10.1007/s00018-015-1835-0. Epub 2015 Jan 11.
Cytotoxic CD8(+) T cells are potent mediators of host protection against disease due to their ability to directly kill cells infected with intracellular pathogens and produce inflammatory cytokines at the site of infection. To fully achieve this objective, naïve CD8(+) T cells must be able to survey the entire body for the presence of foreign or "non-self" antigen that is delivered to draining lymph nodes following infection or tissue injury. Once activated, CD8(+) T cells undergo many rounds of cell division, acquire effector functions, and are no longer restricted to the circulation and lymphoid compartments like their naïve counterparts, but rather are drawn to inflamed tissues to combat infection. As CD8(+) T cells transition from naïve to effector to memory populations, this is accompanied by dynamic changes in the expression of adhesion molecules and chemokine receptors that ultimately dictate their localization in vivo. Thus, an understanding of the molecular mechanisms regulating CD8(+) T cell trafficking and localization is critical for vaccine design, control of infectious diseases, treatment of autoimmune disorders, and cancer immunotherapy.
细胞毒性CD8(+) T细胞是宿主抵御疾病的有力介质,因为它们能够直接杀死被细胞内病原体感染的细胞,并在感染部位产生炎性细胞因子。为了完全实现这一目标,初始CD8(+) T细胞必须能够在全身检测感染或组织损伤后传递至引流淋巴结的外来或“非自身”抗原的存在。一旦被激活,CD8(+) T细胞会经历多轮细胞分裂,获得效应功能,并且不再像初始对应细胞那样局限于循环和淋巴区室,而是被吸引到炎症组织中对抗感染。随着CD8(+) T细胞从初始群体转变为效应群体再到记忆群体,这伴随着黏附分子和趋化因子受体表达的动态变化,这些变化最终决定了它们在体内的定位。因此,了解调节CD8(+) T细胞运输和定位的分子机制对于疫苗设计、传染病控制、自身免疫性疾病治疗以及癌症免疫治疗至关重要。