Expansion of protective CD8+ T-cell responses driven by recombinant cytomegaloviruses
Expansion of protective CD8+ T-cell responses driven by recombinant cytomegaloviruses
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DOI：
10.1128/jvi.78.5.2255-2264.2004
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发表时间：
2004-03-01
影响因子：
5.4
通讯作者：
Klenerman, P
中科院分区：
文献类型：
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作者：
Karrer, U;Wagner, M;Klenerman, P
CD 8（+）T细胞对于控制许多持续性病毒感染至关重要，如人类免疫缺陷病毒、丙型肝炎病毒、EB病毒和巨细胞病毒（CMV）。在大多数感染中，大的CD 8（+）-T细胞群体在早期被诱导，但随后收缩并在此后维持在较低水平。相反，对鼠CMV（MCMV）特异性的CD 8（+）T细胞已显示在原发感染消退后逐渐积累。这种独特的行为仅限于某些表位，包括来自立即早期1（IE 1）基因产物的免疫显性表位。为了进一步探索这背后的机制，我们测量了由来自A型流感病毒或淋巴细胞性脉络丛脑膜炎病毒的重组MCMV表达表位诱导的CD 8（+）-T细胞介导的免疫，这些表位置于IE启动子的控制下。我们观察到病毒特异性CD 8（+）-T细胞群被诱导，并且随着时间的推移逐渐扩增。重要的是，这些CD 8（+）T细胞提供了长期的保护，免受挑战，而无需加强。这些结果证明了积累T细胞的独特模式，其提供持久的免疫保护，其独立于表位的初始免疫优势，并表明基于持久载体的T细胞诱导疫苗的潜力。
CD8(+) T cells are critical for the control of many persistent viral infections, such as human immunodeficiency virus, hepatitis C virus, Epstein-Barr virus, and cytomegalovirus (CMV). In most infections, large CD8(+)-T-cell populations are induced early,but then contract and are maintained thereafter at lower levels. In contrast, CD8(+) T cells specific for murine CMV (MCMV) have been shown to gradually accumulate after resolution of primary infection. This unique behavior is restricted to certain epitopes, including an immunodominant epitope derived from the immediate-early 1 (IE1) gene product. To explore the mechanism behind this further, we measured CD8(+)-T-cell-mediated immunity induced by recombinant MCMV-expressing epitopes derived from influenza A virus or lymphocytic choriomeningitis virus placed under the control of an IE promoter. We observed that virus-specific CD8(+)-T-cell populations were induced and that these expanded gradually over time. Importantly, these CD8(+) T cells provided long-term protection against challenge without boosting. These results demonstrate a unique pattern of accumulating T cells, which provide long-lasting immune protection, that is independent of the initial immunodominance of the epitope and indicates the potential of T-cell-inducing vaccines based on persistent vectors.