白细胞介素-15/白细胞介素-15受体α介导的记忆性CD8 + T细胞亲和力成熟
IL-15/IL-15Ralpha-mediated avidity maturation of memory CD8+ T cells.
作者信息
Oh SangKon, Perera Liyanage P, Burke Donald S, Waldmann Thomas A, Berzofsky Jay A
机构信息
Vaccine Branch and Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15154-9. doi: 10.1073/pnas.0406649101. Epub 2004 Oct 11.
T cell avidity is critical to viral clearance, but mechanisms of CD8(+) T cell avidity maturation are poorly understood. Here, we find that IL-15 mediates two mechanisms of avidity maturation. (i) By selection at the population level, IL-15 promotes greater survival of high- compared with low-avidity cytotoxic T lymphocytes (CTLs). High-avidity CTLs express higher levels of IL-15Ralpha and persist longer by homeostatic proliferation. (ii) At the individual cell level, IL-15 induces higher levels of surface coreceptor CD8alphabeta, increasing functional avidity. IL-15 during priming selects or induces higher-avidity CTLs. Conversely, high-avidity CTLs are diminished in IL-15Ralpha knockout mice. These results provide an explanation of CD8+ T cell avidity maturation and may contribute to the design of novel vaccines.
T细胞亲和力对于病毒清除至关重要，但CD8(+) T细胞亲和力成熟的机制仍知之甚少。在此，我们发现白细胞介素-15（IL-15）介导了亲和力成熟的两种机制。（i）在群体水平上通过选择，与低亲和力细胞毒性T淋巴细胞（CTL）相比，IL-15促进高亲和力CTL的存活。高亲和力CTL表达更高水平的IL-15Rα，并通过稳态增殖持续更长时间。（ii）在个体细胞水平上，IL-15诱导更高水平的表面共受体CD8αβ，增加功能亲和力。启动过程中的IL-15选择或诱导更高亲和力的CTL。相反，在IL-15Rα基因敲除小鼠中，高亲和力CTL数量减少。这些结果解释了CD8+ T细胞亲和力成熟的机制，并可能有助于新型疫苗的设计。
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