Homeostatic Turnover of Virus-Specific Memory CD8 T Cells Occurs Stochastically and Is Independent of CD4 T Cell Help
Homeostatic Turnover of Virus-Specific Memory CD8 T Cells Occurs Stochastically and Is Independent of CD4 T Cell Help
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DOI：
10.4049/jimmunol.1001421
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发表时间：
2010-09-15
影响因子：
4.4
通讯作者：
Ahmed, Rafi
中科院分区：
文献类型：
--
作者：
Choo, Daniel K.;Murali-Krishna, Kaja;Ahmed, Rafi
记忆性CD8 T细胞通过不依赖ag的稳态增殖持续存在。为了研究这种细胞更替的动力学，我们将淋巴细胞性脉络丛脑膜炎病毒特异性记忆CD8 T细胞转移到幼稚小鼠体内，并纵向分析了它们在个体受体体内的分裂动力学。利用数学模型，我们确定这种稳定维持的记忆性CD8 T细胞群的增殖是均匀的和随机的，在任何给定的时间内，一小部分细胞以50天的间歇间隔完成分裂。这种稳态周转在不同病毒表位特异性的记忆性CD8 T细胞和总记忆表型（CD44（高））CD8 T细胞之间是可比较的。众所周知，CD4 T细胞的帮助对慢性感染期间CD8 T细胞的维持至关重要，但最近的研究表明，CD4 T细胞的帮助也需要在急性感染后维持记忆性CD8 T细胞。因此，我们评估了CD4 T细胞在不依赖ag的记忆性CD8 T细胞维持中的作用。与之前的报道一致，我们发现记忆性CD8 T细胞在转移到MHC ii类缺陷小鼠体内时下降。然而，当转移到CD4 T细胞缺陷小鼠体内时，它们的数量保持稳定。有趣的是，当记忆性CD8 T细胞在MHC II类或CD4缺陷受体中转移和维持时，它们的稳态增殖、回忆性反应能力和表型都不依赖于CD4 T细胞的帮助，因为这些品质都不受影响。中华免疫学杂志，2010,18(5):336 -344。
Memory CD8 T cells persist by Ag-independent homeostatic proliferation. To examine the dynamics of this cell turnover, we transferred lymphocytic choriomeningitis virus specific memory CD8 T cells into naive mice and analyzed their in vivo division kinetics longitudinally in individual recipients. Using mathematical modeling, we determined that proliferation of this stably maintained memory CD8 T cell population was homogeneous and stochastic with a small fraction of cells completing division at any given time with an intermitotic interval of 50 d. This homeostatic turnover was comparable between memory CD8 T cells of different viral epitope specificities and also the total memory phenotype (CD44(high)) CD8 T cells. It is well established that CD4 T cell help is critical for maintenance of CD8 T cells during chronic infections, but recent studies have suggested that CD4 T cell help is also required for maintenance of memory CD8 T cells following acute infections. Hence, we assessed the role of CD4 T cells in Ag-independent maintenance of memory CD8 T cells. Consistent with previous reports, we found that memory CD8 T cells declined when transferred into MHC class II-deficient mice. However, their numbers were maintained stably when transferred into CD4 T cell-deficient mice. Interestingly, their homeostatic proliferation, ability to make recall responses, and phenotype were independent of CD4 T cell help because none of these qualities were affected when memory CD8 T cells were transferred and maintained in either MHC class II- or CD4-deficient recipients. The Journal of Immunology, 2010, 185: 3436-3444.