Recognition of HIV-1 infected CD4 T cells by HIV-1 specific CD8 T cells.

HIV-1 特异性 CD8 T 细胞对 HIV-1 感染的 CD4 T 细胞的识别。

• 批准号: 12670284
• 负责人: TOMIYAMA Hiroko
• 金额: $ 1.98万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670284/
• 关键词: CD8 T cell; inhibition of HIV-1 replication; cytokine; cytotoxic activity; HLA-Class I; down-regulation; nef; escape; 細胞傷害活性; Nef; HIV-1; 特異的CD8 T細胞; テトラマー; perforin; エフェクター細胞

Despite the high frequency of HIV-1 specific CD8^+ T cells were detected, no HIV-1 infected individuals has been ever known to clear away the virus from their body. The mechanism of HIV-1 escape from the recognition of CD8^+ T cells is still unclear. Previous report has demonstrated that primary CD4^+ T cells infected with nef^+ HIV-1 down regulate surface HLA-Class I antigens and are resistant to lysis by HIV-1 specific CTL clones. However it is not unclear whether CTL can recognize HIV-1 infected cells or not. In this study we indicated that HIV-1 specific CTL clones were not able to kill the purified CD4^+ T cells infected with nef ^+ HIV-1(NL-432), while they efficiently lysed CD4^+ T cells infected with nef mutant HIV-1 (NL-M20A) which express functional Nef protein but does not induce the down-regulation of HLA-Class I molecules on infected cells. Cytokine production of these CTL clones by stimulation with NL-432 infected CD4^+ T cells were lower than that by stimulation with NL-M20A infected T cells. These results indicate that the effect of Nef-mediated HLA-Class I down-regulation on infected cells is more affective for killing activity of CTL than that for cytokine production of CTL. Although the replication of NL-M20A was completely suppressed in direct coculture of CTL clone with infected cells, the suppression of NL-432 replication by CTL clone was 50%. These results suggested that HIV-1 specific CD8^+ T cells may partially suppress the replication of nef^+ HIV-1 by production of soluble antiviral factors such as chemokine and cytokine. These findings may explain why HIV-1 specific CD8^+ T cells can control HIV-1 replication in vivo but not completely suppressed HIV-1 replication.

尽管HIV-1特异性CD 8 ^+ T细胞的出现频率很高，但迄今为止还没有发现HIV-1感染者能够清除体内的病毒。HIV-1逃避CD 8 ^+ T细胞识别的机制尚不清楚。先前的报道已经证明，感染nef^+ HIV-1的原代CD 4 ^+ T细胞下调表面HLA-I类抗原，并且对HIV-1特异性CTL克隆的裂解具有抗性。然而，CTL是否能识别HIV-1感染的细胞尚不清楚。在这项研究中，我们发现HIV-1特异性CTL克隆不能杀死nef ^+ HIV-1（NL-432）感染的纯化的CD 4 ^+ T细胞，而它们能有效地裂解nef突变型HIV-1（NL-M20 A）感染的CD 4 ^+ T细胞，后者表达功能性Nef蛋白，但不诱导感染细胞上HLA-I类分子的下调。用NL-432感染的CD 4 ^+ T细胞刺激这些CTL克隆产生的细胞因子低于用NL-M20 A感染的T细胞刺激。这些结果表明，Nef介导的HLA-I类下调对感染细胞的影响对CTL的杀伤活性比对CTL的细胞因子产生更有效。CTL克隆与感染细胞直接共培养时，NL-M20 A的复制被完全抑制，而CTL克隆对NL-432复制的抑制为50%。这些结果表明HIV-1特异性CD 8 ^+ T细胞可能通过产生可溶性抗病毒因子如趋化因子和细胞因子部分抑制nef^+ HIV-1的复制。这些发现可以解释为什么HIV-1特异性CD 8 ^+ T细胞可以控制HIV-1在体内的复制，但不能完全抑制HIV-1的复制。

项目成果

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