Role of CD28 co-stimulation in generation and maintenance of virus-specific T cells
Role of CD28 co-stimulation in generation and maintenance of virus-specific T cells
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DOI：
10.1093/intimm/dxf037
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发表时间：
2002-07-01
影响因子：
4.4
通讯作者：
Thomsen, AR
中科院分区：
文献类型：
--
作者：
Christensen, JE;Christensen, JP;Thomsen, AR
T细胞反应的有效诱导通常被认为需要TCR介导的信号和共刺激分子的参与，特别是CD28。然而，CD28共刺激在诱导和维持抗病毒T细胞反应中的重要性尚不清楚。为此，用两种不同的病毒[水泡性口炎病毒和淋巴细胞性脉络膜脑膜炎病毒(LCMV)]研究了CD28缺陷小鼠的抗病毒CD4(+)和CD8(+)T细胞反应。细胞内细胞因子染色和/或MHC多肽四聚体计数抗原特异性T细胞。此外，我们使用编码病毒表位的DNA结构来探索表位本身的重要性。我们的结果表明，虽然抗原提呈的背景(活病毒与DNA构建)是决定CD28共刺激需求的关键因素，但表位和病毒剂量几乎没有作用。抗原特异性细胞的直接可视化也证实了CD28对于产生抗病毒T(H)1细胞比对同一病毒(LCMV)产生的T(C)1细胞更关键的概念。最重要的是，本研究揭示了CD28对于宿主在广泛的条件下做出最佳反应通常是必不可少的，我们的结果可能意味着相对CD28独立的LCMV特异性CD8(+)T细胞的激活可能代表了与这种病毒的非细胞溶解性质有关的极端情况，从而允许传递独特的强而持久的信号1。
Efficient induction of T cell responses is normally assumed to require both TCR-mediated signaling and engagement of co-stimulatory molecules, in particular CD28. However, the importance of CD28 co-stimulation in induction and maintenance of antiviral T cell responses is not clearly established. For this reason antiviral CD4(+) and CD8(+) T cell responses in CD28-deficient mice were studied using two different viruses [vesicular stomatitis virus and lymphocytic choriomeningitis virus (LCMV)]. Intracellular cytokine staining and/or MHC-peptide tetramers were used to enumerate antigen-specific T cells. In addition, we used DNA constructs encoding viral epitopes to probe the importance of the epitope itself. Our results reveal that while the context of antigen presentation (live virus versus DNA construct) is a critical factor in determining the requirement for CD28 co-stimulation, epitope and virus dose play little if any role. Direct visualization of antigen-specific cells also confirms the notion that CD28 is more critical for the generation of antiviral T(h)1 cells than for T(c)1 cells generated in response to the same virus (LCMV). Most importantly, the present study reveals that CD28 generally is essential for the host to respond optimally over a broad set of conditions, and our results may imply that the relatively CD28 independent activation of LCMV-specific CD8(+) T cells may represent an extreme situation related to the non-cytolytic nature of this virus allowing the delivery of a uniquely strong and prolonged signal 1.