The yellow fever virus vaccine induces a broad and polyfunctional human memory CD8+ T cell response.
The yellow fever virus vaccine induces a broad and polyfunctional human memory CD8+ T cell response.
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DOI：
10.4049/jimmunol.0803903
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发表时间：
2009-12-15
期刊：
影响因子：
--
通讯作者：
Ahmed R
中科院分区：
文献类型：
--
作者：
Akondy RS;Monson ND;Miller JD;Edupuganti S;Teuwen D;Wu H;Quyyumi F;Garg S;Altman JD;Del Rio C;Keyserling HL;Ploss A;Rice CM;Orenstein WA;Mulligan MJ;Ahmed R
黄热病活疫苗（YF-17D）为研究急性病毒感染后人类记忆性CD8 + T细胞分化提供了独特的机会。我们已经使用跨越整个病毒基因组的重叠肽对病毒特异性CD8 + T细胞应答进行了全面分析。我们的结果表明，YF-17D疫苗诱导广泛的CD8 + T细胞应答，靶向每种病毒蛋白内的几个表位。我们在NS4B蛋白中鉴定了一个显性HLA-A2限制性表位，并使用对该表位特异的四聚体在2年内追踪CD8 + T细胞应答。这一纵向分析显示了以下情况。1)记忆性CD8 + T细胞似乎通过效应期，然后逐渐下调活化标志物和效应分子的表达。2)该效应期的特征是CD 127、Bcl-2、CCR 7和CD 45 RA的下调，随后出现大幅收缩，产生重新表达CD 127、Bcl-2和CD 45 RA的记忆T细胞库。3)这些记忆细胞在脱颗粒和产生细胞因子IFN-γ、TNF-α、IL-2和MIP-1 β方面是多功能的。4)YF-17 D特异性记忆CD8 + T细胞具有典型的增殖能力有限的终末分化细胞（TEMRA）相关的表型（CCR7 − CD45 RA+）。然而，这些细胞表现出强大的增殖潜力，表明CD45RA的表达可能并不总是与终末分化相关，事实上，可能是急性病毒感染后产生的高功能记忆CD8 + T细胞的指标。
The live yellow fever vaccine (YF-17D) offers a unique opportunity to study memory CD8+ T cell differentiation in humans following an acute viral infection. We have performed a comprehensive analysis of the virus-specific CD8+ T cell response using overlapping peptides spanning the entire viral genome. Our results showed that the YF-17D vaccine induces a broad CD8+ T cell response targeting several epitopes within each viral protein. We identified a dominant HLA-A2-restricted epitope in the NS4B protein and used tetramers specific for this epitope to track the CD8+ T cell response over a 2 year period. This longitudinal analysis showed the following. 1) Memory CD8+ T cells appear to pass through an effector phase and then gradually down-regulate expression of activation markers and effector molecules. 2) This effector phase was characterized by down-regulation of CD127, Bcl-2, CCR7, and CD45RA and was followed by a substantial contraction resulting in a pool of memory T cells that re-expressed CD127, Bcl-2, and CD45RA. 3) These memory cells were polyfunctional in terms of degranulation and production of the cytokines IFN-γ, TNF-α, IL-2, and MIP-1β. 4) The YF-17D-specific memory CD8+ T cells had a phenotype (CCR7−CD45RA+) that is typically associated with terminally differentiated cells with limited proliferative capacity (TEMRA). However, these cells exhibited robust proliferative potential showing that expression of CD45RA may not always associate with terminal differentiation and, in fact, may be an indicator of highly functional memory CD8+ T cells generated after acute viral infections.
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