Ishii Hiroshi, Matsuoka Saori, Nomura Takushi, Nakamura Midori, Shiino Teiichiro, Sato Yuko, Iwata-Yoshikawa Naoko, Hasegawa Hideki, Mizuta Kazuta, Sakawaki Hiromi, Miura Tomoyuki, Koyanagi Yoshio, Naruse Taeko K, Kimura Akinori, Matano Tetsuro
AIDS Research Center, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.
Center for AIDS Research, Kumamoto University, Tokyo 162-8640, Japan.
Sci Rep. 2016 Jul 25;6:30153. doi: 10.1038/srep30153.
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.
病毒特异性CD8(+) T细胞对人类/猴免疫缺陷病毒（HIV/SIV）复制施加强大的抑制压力。这些反应已在外周血单核细胞（PBMC）中进行了深入研究，但在淋巴结（LN）中尚未得到充分分析，而CD8(+) T细胞与HIV/SIV感染细胞之间的相互作用发生在淋巴结中。在此，我们在猕猴艾滋病模型中研究了淋巴结中CD8(+) T细胞的靶抗原特异性。对从20只处于SIV感染慢性期的恒河猴腹股沟淋巴结中获得的病毒抗原特异性CD8(+) T细胞反应进行分析，结果显示病毒载量与靶向SIV核心抗原（Gag-N）N端一半的具有CD28(+) CD95(+) 中央记忆表型的CD8(+) T细胞频率呈负相关。相比之下，对淋巴结而非PBMC的分析显示，病毒载量与靶向SIV包膜（Env-N）N端一半的可溶性抗原、具有CD28(-)CD95(+) 效应记忆表型的CD8(+) T细胞频率呈正相关。事实上，生发中心可检测到SIV衣壳p27抗原的淋巴结，与未检测到p27的淋巴结相比，Gag-N特异性CD28(+) CD95(+) CD8(+) T细胞反应显著降低，而Env-N特异性CD28(-)CD95(+) CD8(+) T细胞反应更高。这些结果表明，核心抗原和包膜抗原特异性CD8(+) T细胞与HIV/SIV感染细胞的相互作用模式不同。
