Departments of Microbiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
Indian J Med Res. 2010 Sep;132:318-27.
BACKGROUND & OBJECTIVES: DCs trigger both innate and adaptive immune responses to control HIV infection and represent a viral reservoir acting as target and HIV carriers for infection of permissive CD4(+) T-cells. DCs thus form a very attractive study subject to further our existing knowledge of HIV induced immunopathogenesis due to its diverse and crucial role in HIV infection establishment, viral dissemination, immune evasion, viral persistence, etc. We aimed to characterize the effect of HIV infection on myeloid and plasmacytoid dendritic cell subsets in a group of HIV-1 subtype C infected treated or untreated Indian individuals.
Blood DC subset numbers and immunophenotype were studied for 79 HIV infected subjects at various stages of disease and compared with 13 HIV-uninfected controls. Comparisons were also made between groups of subjects based on their CD4(+) T cell counts and also experience of antiretrovirals.
Significant decreases were observed in blood DC counts and the two DC subsets in HIV infected individuals. Subjects with lowest CD4(+) T cell counts also had a drastically reduced DC subset pool which correlated positively with plasma viraemia and negatively with CD4(+) T cell counts. DC subsets from HIV infected subjects showed higher expression of co-stimulatory molecules CD40 and CD86, and HIV-1 co-receptors CXCR4 and CCR5 which correlated positively with HIV-1 plasma viraemia. The alterations in blood DCs were partly resolved in ART receiving study subjects.
INTERPRETATION & CONCLUSIONS: Correlation between DC subset activation state and viraemia supports the role of DC activation on viral replication and CD4(+) T cell depletion.
树突状细胞(DC)既能引发固有免疫反应,也能引发适应性免疫反应,从而控制 HIV 感染,成为病毒储存库,既能作为靶细胞,也能作为感染许可性 CD4+T 细胞的 HIV 载体。因此,DC 是一个非常有吸引力的研究对象,可以进一步了解 HIV 诱导的免疫发病机制,因为它在 HIV 感染的建立、病毒传播、免疫逃逸、病毒持续存在等方面具有多样化且至关重要的作用。我们旨在描述 HIV 感染对一组接受或未接受治疗的 HIV-1 型 C 亚型感染的印度个体的髓系和浆细胞样树突状细胞亚群的影响。
研究了 79 名处于不同疾病阶段的 HIV 感染者和 13 名 HIV 未感染者的血液树突状细胞亚群数量和免疫表型,并进行了比较。还根据 CD4+T 细胞计数和抗逆转录病毒药物的使用经验,对各组受试者进行了比较。
在 HIV 感染者中,血液树突状细胞计数和两种树突状细胞亚群均显著减少。CD4+T 细胞计数最低的受试者的树突状细胞亚群池也急剧减少,与血浆病毒血症呈正相关,与 CD4+T 细胞计数呈负相关。HIV 感染者的树突状细胞亚群表现出更高的共刺激分子 CD40 和 CD86,以及 HIV-1 共受体 CXCR4 和 CCR5 的表达,与 HIV-1 血浆病毒血症呈正相关。接受 ART 的研究受试者的血液树突状细胞的改变部分得到了缓解。
树突状细胞亚群激活状态与病毒血症之间的相关性支持树突状细胞激活在病毒复制和 CD4+T 细胞耗竭中的作用。