Association of lymph-node antigens with lower Gag-specific central-memory and higher Env-specific effector-memory CD8(+) T-cell frequencies in a macaque AIDS model.
Association of lymph-node antigens with lower Gag-specific central-memory and higher Env-specific effector-memory CD8(+) T-cell frequencies in a macaque AIDS model.
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DOI：
10.1038/srep30153
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发表时间：
2016-07-25
影响因子：
4.6
通讯作者：
Matano T
中科院分区：
文献类型：
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作者：
Ishii H;Matsuoka S;Nomura T;Nakamura M;Shiino T;Sato Y;Iwata-Yoshikawa N;Hasegawa H;Mizuta K;Sakawaki H;Miura T;Koyanagi Y;Naruse TK;Kimura A;Matano T
病毒特异性CD8+T细胞对人类/猴免疫缺陷病毒(HIV/SIV)复制具有很强的抑制作用。这些反应已经在外周血单个核细胞(PBMC)中得到了深入的研究，但在CD8+T细胞和HIV/SIV感染细胞之间发生相互作用的淋巴结中还没有完全分析。在这里，我们在猕猴艾滋病模型中研究了LNS中CD8+T细胞的靶抗原特异性。对20只SIV感染慢性期恒河猴腹股沟淋巴结中病毒抗原特异性CD8+T细胞反应的分析表明，病毒载量与针对SIV核心抗原N端半部分(Gag-N)的CD28+CD95+中央记忆表型的CD8+T细胞的频率呈负相关。相反，对LN而不是PBMC的分析显示，针对SIV包膜N-末端半部分(−-N)的CD28SIV CD95+效应记忆表型与病毒载量和CD8+T细胞频率呈正相关。事实上，在生发中心有SIV衣壳p27抗原的淋巴结比那些没有检测到p27的淋巴结表现出更低的GAG-N特异性CD28+CD95+CD8+T细胞和更高的Env-N特异性CD28−CD95+CD8+T细胞应答。这些结果表明，核心抗原和包膜抗原特异的CD8+T细胞与HIV/SIV感染细胞表现出不同的相互作用模式。
Virus-specific CD8+ T cells exert strong suppressive pressure on human/simian immunodeficiency virus (HIV/SIV) replication. These responses have been intensively examined in peripheral blood mononuclear cells (PBMCs) but not fully analyzed in lymph nodes (LNs), where interaction between CD8+ T cells and HIV/SIV-infected cells occurs. Here, we investigated target antigen specificity of CD8+ T cells in LNs in a macaque AIDS model. Analysis of virus antigen-specific CD8+ T-cell responses in the inguinal LNs obtained from twenty rhesus macaques in the chronic phase of SIV infection showed an inverse correlation between viral loads and frequencies of CD8+ T cells with CD28+ CD95+ central memory phenotype targeting the N-terminal half of SIV core antigen (Gag-N). In contrast, analysis of LNs but not PBMCs revealed a positive correlation between viral loads and frequencies of CD8+ T cells with CD28−CD95+ effector memory phenotype targeting the N-terminal half of SIV envelope (Env-N), soluble antigen. Indeed, LNs with detectable SIV capsid p27 antigen in the germinal center exhibited significantly lower Gag-N-specific CD28+ CD95+ CD8+ T-cell and higher Env-N-specific CD28−CD95+ CD8+ T-cell responses than those without detectable p27. These results imply that core and envelope antigen-specific CD8+ T cells show different patterns of interactions with HIV/SIV-infected cells.