CD4+而非CD8+ T细胞克隆产生内源性β趋化因子，这与人类免疫缺陷病毒1型（HIV-1）感染者的临床状态相关，并且可能是体外阻断非合胞体诱导型HIV-1感染的原因。
Endogenous production of beta-chemokines by CD4+, but not CD8+, T-cell clones correlates with the clinical state of human immunodeficiency virus type 1 (HIV-1)-infected individuals and may be responsible for blocking infection with non-syncytium-inducing HIV-1 in vitro.
作者信息
Saha K, Bentsman G, Chess L, Volsky D J
机构信息
Molecular Virology Laboratory, St. Luke's-Roosevelt Hospital Center, College of Physicians & Surgeons, Columbia University, New York, New York 10019, USA.
出版信息
J Virol. 1998 Jan;72(1):876-81. doi: 10.1128/JVI.72.1.876-881.1998.
Recent studies have demonstrated that the beta-chemokines RANTES, MIP-1alpha, and MIP-1beta suppress human immunodeficiency virus type 1 (HIV-1) replication in vitro and may play an important role in protecting exposed but uninfected individuals from HIV-1 infection. However, levels of beta-chemokines in AIDS patients are comparable to and can exceed levels in nonprogressing individuals, indicating that global beta-chemokine production may have little effect on HIV-1 disease progression. We sought to clarify the role of beta-chemokines in nonprogressors and AIDS patients by examination of beta-chemokine production and HIV-1 infection in patient T-lymphocyte clones established by herpesvirus saimiri immortalization. Both CD4+ and CD8+ clones were established, and they resembled primary T cells in their phenotypes and expression of activated T-cell markers. CD4+ T-cell clones from all patients had normal levels of mRNA-encoding CCR5, a coreceptor for non-syncytium-inducing (NSI) HIV-1. CD4+ clones from nonprogressors and CD8+ clones from AIDS patients secreted high levels of RANTES, MIP1alpha, and MIP-1beta. In contrast, CD4+ clones from AIDS patients produced no RANTES and little or no MIP-1alpha or MIP-1beta. The infection of CD4+ clones with the NSI HIV-1 strain ADA revealed an inverse correlation to beta-chemokine production; clones from nonprogressors were poorly susceptible to ADA replication, but clones from AIDS patients were highly infectable. The resistance to ADA infection in CD4+ clones from nonprogressors could be partially reversed by treatment with anti-beta-chemokine antibodies. These results indicate that CD4+ cells can be protected against NSI-HIV-1 infection in culture through endogenously produced factors, including beta-chemokines, and that beta-chemokine production by CD4+, but not CD8+, T cells may constitute one mechanism of disease-free survival for HIV-1-infected individuals.
最近的研究表明，β趋化因子RANTES、MIP-1α和MIP-1β在体外可抑制1型人类免疫缺陷病毒（HIV-1）复制，并且在保护暴露但未感染个体免受HIV-1感染方面可能发挥重要作用。然而，艾滋病患者体内β趋化因子水平与病情无进展个体相当，甚至可能更高，这表明整体β趋化因子产生对HIV-1疾病进展可能影响不大。我们试图通过检测由赛米利疱疹病毒永生化建立的患者T淋巴细胞克隆中β趋化因子的产生及HIV-1感染情况，来阐明β趋化因子在病情无进展者和艾滋病患者中的作用。我们建立了CD4⁺和CD8⁺克隆，它们在表型和活化T细胞标志物表达方面类似于原代T细胞。所有患者的CD4⁺ T细胞克隆中编码CCR5（非合胞体诱导型（NSI）HIV-1的一种共受体）的mRNA水平正常。病情无进展者的CD4⁺克隆以及艾滋病患者的CD8⁺克隆分泌高水平的RANTES、MIP1α和MIP-1β。相比之下，艾滋病患者的CD4⁺克隆不产生RANTES，且几乎不产生或不产生MIP-1α或MIP-1β。用NSI HIV-1毒株ADA感染CD4⁺克隆发现，其与β趋化因子产生呈负相关；病情无进展者的克隆对ADA复制的敏感性低，但艾滋病患者的克隆具有高度感染性。用抗β趋化因子抗体处理可部分逆转病情无进展者CD4⁺克隆对ADA感染的抗性。这些结果表明，在培养中CD4⁺细胞可通过内源性产生的因子（包括β趋化因子）免受NSI-HIV-1感染，并且CD4⁺而非CD8⁺ T细胞产生β趋化因子可能是HIV-1感染个体无病生存的一种机制。
Zotero 插件