Priming of CD8+ T Cells against Cytomegalovirus-Encoded Antigens Is Dominated by Cross-Presentation
Priming of CD8+ T Cells against Cytomegalovirus-Encoded Antigens Is Dominated by Cross-Presentation
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DOI：
10.4049/jimmunol.1200966
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发表时间：
2013-03-15
影响因子：
4.4
通讯作者：
Messerle, Martin
中科院分区：
文献类型：
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作者：
Busche, Andreas;Jirmo, Adan Chari;Messerle, Martin
巨细胞病毒可以感染树突状细胞（dc），因此，直接的银呈递可能导致CMV特异性CD8(+) T细胞的启动。然而，cmv编码的免疫逃避严重损害MHC I类途径中的Ag呈递；因此，人们普遍认为交叉呈递驱动抗病毒T细胞的启动。我们评估了直接引物与交叉引物在重组病毒感染小鼠巨细胞病毒（MCMV）中的作用。用编码HSV-1中gB（498）表位的MCMV菌株感染的dc不能刺激TCR转基因小鼠的体外幼稚gB（498）特异性CD8(+) T细胞。然而，用该重组病毒感染C57BL/6小鼠，可在体内产生大量gb498特异性T细胞。在从感染小鼠中分离的DC亚群中，只有CD8 α (+) DC能够刺激幼稚T细胞，这表明该DC亚群在体内交叉呈现mcmv编码的Ag。编码Ag的MCMV突变体感染小鼠后，产生的抗原表位特异性CD8(+) T细胞主要针对交叉呈递表位。此外，即使没有免疫逃避基因干扰MHC i类介导的银呈递，也没有观察到T细胞对只能直接呈递的银的启动。我们得出结论，宿主主要使用能够交叉呈递的dc在原发性急性感染期间诱导CMV特异性CD8(+) T细胞反应，并讨论了开发CMV疫苗的意义。中华免疫学杂志，2013,19(2):767- 777。
CMV can infect dendritic cells (DCs), and direct Ag presentation could, therefore, lead to the priming of CMV-specific CD8(+) T cells. However, CMV-encoded immune evasins severely impair Ag presentation in the MHC class I pathway; thus, it is widely assumed that cross-presentation drives the priming of antiviral T cells. We assessed the contribution of direct versus cross priming in mouse CMV (MCMV) infection using recombinant viruses. DCs infected with an MCMV strain encoding the gB(498) epitope from HSV-1 were unable to stimulate in vitro naive gB(498)-specific CD8(+) T cells from TCR transgenic mice. Infection of C57BL/6 mice with this recombinant virus led, however, to the generation of abundant numbers of gB498-specific T cells in vivo. Of the DC subsets isolated from infected mice, only CD8 alpha(+) DCs were able to stimulate naive T cells, suggesting that this DC subset cross-presents MCMV-encoded Ag in vivo. Upon infection of mice with MCMV mutants encoding Ag that can either be well or hardly cross-presented, mainly CD8(+) T cells specific for cross-presented epitopes were generated. Moreover, even in the absence of immune evasion genes interfering with MHC class I-mediated Ag presentation, priming of T cells to Ag that can only be presented directly was not observed. We conclude that the host uses mainly DCs capable of cross-presentation to induce the CMV-specific CD8(+) T cell response during primary, acute infection and discuss the implications for the development of a CMV vaccine. The Journal of Immunology, 2013, 190: 2767-2777.