Chemokine-guided CD4+ T cell help enhances generation of IL-6RαhighIL-7Rαhigh prememory CD8+ T cells
Chemokine-guided CD4+ T cell help enhances generation of IL-6RαhighIL-7Rαhigh prememory CD8+ T cells
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DOI：
10.4049/jimmunol.178.2.778
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发表时间：
2007-01-15
影响因子：
4.4
通讯作者：
Germain, Ronald N.
中科院分区：
文献类型：
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作者：
Castellino, Flora;Germain, Ronald N.
CD 4（+）T细胞促进有效的CD 8（+）T细胞介导的免疫，但这种帮助的时间和机制细节仍然存在争议。此外，先天刺激在多大程度上独立于增强CD 8（+）T细胞应答的帮助而起作用也未得到解决。在免疫活性小鼠中使用非感染性疫苗模型，我们表明，即使在先天刺激的存在下，CD 4（+）T细胞在引发后早期的帮助是产生功能记忆CD 8（+）T细胞的最佳池所必需的。CD 4（+）T细胞帮助在引发后不久增加了先前未报道的IL-6 R α（IL）-I-高-7R α（高）前记忆CD 8（+）T细胞群体的大小，其在体内显示出存活优势，并在收缩期后促成了大多数功能性记忆CD 8（+）T细胞。雅阁与我们最近证实的趋化因子引导幼稚CD 8（+）T细胞募集到CD 4（+）T细胞-树突状细胞相互作用的位点一致，IL-6 R α（IL）-I-高-7 R α（高）前记忆以及功能性记忆CD 8（+）T细胞的产生依赖于炎性趋化因子CCL 3和CCL 4的早期接种后作用。总之，这些发现支持了CD 8（+）T细胞记忆细胞分化的模型，该模型涉及基于趋化因子引导的幼稚CD 8（+）T细胞向TLR激活的树突状细胞和CD 4（+）T细胞之间Ag驱动的相互作用位点的吸引，在引发过程早期递送关键信号。他们还揭示了CD 8（+）T细胞亚群的IL-6 R α表达升高代表了CD 4（+）T细胞辅助功能的早期印记，其积极促进活化的CD 8（+）T细胞的存活。
CD4(+) T cells promote effective CD8(+) T cell-mediated immunity, but the timing and mechanistic details of such help remain controversial. Furthermore, the extent to which innate stimuli act independently of help in enhancing CD8(+) T cell responses is also unresolved. Using a noninfectious vaccine model in immunocompetent mice, we show that even in the presence of innate stimuli, CD4(+) T cell help early after priming is required for generating an optimal pool of functional memory CD8(+) T cells. CD4(+) T cell help increased the size of a previously unreported population of IL-6R alpha(IL)-I-high-7R alpha(high) prememory CD8(+) T cells shortly after priming that showed a survival advantage in vivo and contributed to the majority of functional memory CD8(+) T cells after the contraction phase. In accord with our recent demonstration of chemokine-guided recruitment of naive CD8(+) T cells to sites of CD4(+) T cell-dendritic cell interactions, the generation of IL-6R alpha(IL)-I-high-7R alpha(high) prememory as well as functional memory CD8(+) T cells depended on the early postvaccination action of the inflammatory chemokines CCL3 and CCL4. Together, these findings support a model of CD8(+) T cell memory cell differentiation involving the delivery of key signals early in the priming process based on chemokine-guided attraction of naive CD8(+) T cells to sites of Ag-driven interactions between TLR-activated dendritic cells and CD4(+) T cells. They also reveal that elevated IL-6R alpha expression by a subset of CD8(+) T cells represents an early imprint of CD4(+) T cell helper function that actively contributes to the survival of activated CD8(+) T cells.