Strong Ability of Nef-Specific CD4+ Cytotoxic T Cells To Suppress Human Immunodeficiency Virus Type 1 (HIV-1) Replication in HIV-1-Infected CD4+ T Cells and Macrophages
Strong Ability of Nef-Specific CD4+ Cytotoxic T Cells To Suppress Human Immunodeficiency Virus Type 1 (HIV-1) Replication in HIV-1-Infected CD4+ T Cells and Macrophages
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Nef 特异性 CD4 细胞毒性 T 细胞抑制人类免疫缺陷病毒 1 型 (HIV-1) 在 HIV-1 感染的 CD4 T 细胞和巨噬细胞中复制的强大能力
作者：
Nan Zheng;M. Fujiwara;T. Ueno;S. Oka;M. Takiguchi
摘要有限数量的研究表明，人类免疫缺陷病毒1型（HIV-1）特异性细胞毒性CD 4 + T细胞存在于HIV-1感染的个体中。然而，这种类型的CD 4 + T细胞在针对HIV-1感染的免疫应答中的作用仍不清楚。在这项研究中，我们确定了新的Nef表位特异性HLA-DRB 1 *0803限制性细胞毒性CD 4 + T细胞。Nef 187 -203特异性的CD 4 + T细胞克隆在用表达Nef的重组牛痘病毒感染的自体B淋巴母细胞刺激或用热灭活病毒颗粒脉冲刺激后显示出强烈的γ干扰素产生，表明表位抗原通过外源性和内源性主要组织相容性复合物II类加工途径呈递。Nef 187 -203特异性CD 4 + T细胞克隆对HIV-1感染的巨噬细胞和来自HLA-DRB 1 *0803+供体的CD 4 + T细胞均表现出强细胞毒活性。此外，这些Nef特异性细胞毒性CD 4 + T细胞克隆在体外表现出很强的抑制HIV-1在巨噬细胞和CD 4 + T细胞中复制的能力。Nef 187 -203特异性细胞毒性CD 4 + T细胞分别在40%和20%的DRB 1 *0803+供体的肽刺激的外周血单核细胞（PBMC）培养物和离体PBMC中检测到。这些结果表明，HIV-1特异性CD 4 + T细胞可能通过抑制HIV-1天然宿主细胞中的病毒复制来直接控制体内HIV-1感染。
ABSTRACT A restricted number of studies have shown that human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic CD4+ T cells are present in HIV-1-infected individuals. However, the roles of this type of CD4+ T cell in the immune responses against an HIV-1 infection remain unclear. In this study, we identified novel Nef epitope-specific HLA-DRB1*0803-restricted cytotoxic CD4+ T cells. The CD4+ T-cell clones specific for Nef187-203 showed strong gamma interferon production after having been stimulated with autologous B-lymphoblastoid cells infected with recombinant vaccinia virus expressing Nef or pulsed with heat-inactivated virus particles, indicating the presentation of the epitope antigen through both exogenous and endogenous major histocompatibility complex class II processing pathways. Nef187-203-specific CD4+ T-cell clones exhibited strong cytotoxic activity against both HIV-1-infected macrophages and CD4+ T cells from an HLA-DRB1*0803+ donor. In addition, these Nef-specific cytotoxic CD4+ T-cell clones exhibited strong ability to suppress HIV-1 replication in both macrophages and CD4+ T cells in vitro. Nef187-203-specific cytotoxic CD4+ T cells were detected in cultures of peptide-stimulated peripheral blood mononuclear cells (PBMCs) and in ex vivo PBMCs from 40% and 20% of DRB1*0803+ donors, respectively. These results suggest that HIV-1-specific CD4+ T cells may directly control HIV-1 infection in vivo by suppressing virus replication in HIV-1 natural host cells.
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影响因子：
56.9
作者：
Ogg, GS;Jin, X;McMichael, AJ
通讯作者：
McMichael, AJ
影响因子：
56.9
作者：
Rosenberg, ES;Billingsley, JM;Walker, BD
通讯作者：
Walker, BD
CD4 T 细胞的穿孔素依赖性细胞毒活性和淋巴因子分泌受 CD8 T 细胞调节。
DOI：
--
发表时间：
1997
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Williams,NS;Engelhard,VH
通讯作者：
Engelhard,VH
影响因子：
3.7
作者：
Kaur, Gurvinder;Tuen, Michael;Hioe, Catarina E.
通讯作者：
Hioe, Catarina E.
影响因子：
3.7
作者：
Green, S;Kurane, I;Ennis, FA
通讯作者：
Ennis, FA