Spontaneous and antigen-induced production of HIV-inhibitory β-chemokines are associated with AIDS-free status
Spontaneous and antigen-induced production of HIV-inhibitory β-chemokines are associated with AIDS-free status
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DOI：
10.1073/pnas.96.21.11986
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发表时间：
1999-10-12
影响因子：
11.1
通讯作者：
Gallo, RC
中科院分区：
文献类型：
--
作者：
Garzino-Demo, A;Moss, RB;Gallo, RC
β-趋化因子RANTES、巨噬细胞炎症蛋白(MIP)-1α和MIP-1β通过结合和下调病毒共受体CCR5来抑制嗜巨噬细胞株HIV和猴免疫缺陷病毒(SIV)的感染。因此，我们研究了较高水平的CCR5配体是否与艾滋病患者更有利的临床状态相关。对巴尔的摩多中心艾滋病队列研究的100名受试者进行了横断面研究，以测量外周血单个核细胞(PBMC)趋化因子的产生和淋巴细胞的增殖。对数据的统计分析表明，HIV抗原刺激的PBMC产生的HIV抑制性β-趋化因子在HIV阳性的非艾滋病患者中显著高于临床艾滋病患者。趋化因子的产生增加也与对HIV抗原更高的增殖反应相关。与非艾滋病组相比，艾滋病组的这两个参数都显著降低。值得注意的是，与血清阳性和非多中心艾滋病队列研究血清阴性的受试者相比，来自HIV感染风险释放的血清阴性受试者的未刺激的PBMC中MIP-1α的水平也显著升高。趋化因子的产生与抗原诱导的增殖反应、HIV感染中更有利的临床状态以及感染高危人群中的未感染状态相关联，表明这些分子在控制HIV感染的自然过程中发挥了积极作用。
The beta-chemokines RANTES, macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta suppress infection by macrophage-tropic strains of HIV and simian immunodeficiency virus (SIV) by binding and down-regulating the viral coreceptor, CCR5. Accordingly, we have examined whether higher levels of CCR5 ligands are associated with a more favorable clinical status in AIDS. A cross-sectional study of 100 subjects enrolled in the Multicenter AIDS Cohort Study at the Baltimore site was conducted to measure chemokine production and lymphocyte proliferation by peripheral blood mononuclear cells (PBMC). Statistical analyses of the data revealed that the production of HIV-suppressive beta-chemokines by HIV antigen-stimulated PBMC was significantly higher in HIV-positive subjects without AIDS compared with subjects with clinical AIDS. increased chemokine production was also correlated with higher proliferative responses to HIV antigens. Both parameters were significantly lower in the AIDS versus non-AIDS group. Notably, significantly higher revels of MIP-1 alpha were also observed with unstimulated PBMC from seronegative subjects at risk for HIV infection released as compared with seropositive and non-Multicenter AIDS Cohort Study seronegative subjects. The association of chemokine production with antigen-induced proliferative responses, more favorable clinical status in HIV infection, as well as with an uninfected status in subjects at risk for infection suggests a positive role for these molecules in controlling the natural course of HIV infection.