Retroviral Genetics Division, Center for Virus Research, Westmead Millennium Institute, Westmead Hospital, The University of Sydney, Westmead, NSW, Sydney, Australia.
BMC Infect Dis. 2009 Dec 2;9:192. doi: 10.1186/1471-2334-9-192.
HIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). But the role of cellular infiltration and activation together with HIV in the development of HAD is poorly understood.
To study activation and infiltration patterns of macrophages, CD8+ T cells in relation to HIV in diverse CNS areas of patients with and without dementia. 46 brain regions from two rapidly progressing severely demented patients and 53 regions from 4 HIV+ non-dementia patients were analyzed. Macrophage and CD8+ T cell infiltration of the CNS in relation to HIV was assessed using immuno-histochemical analysis with anti-HIV (P24), anti-CD8 and anti-CD68, anti-S-100A8 and granzyme B antibodies (cellular activation). Statistical analysis was performed with SPSS 12.0 with Student's t test and ANOVA.
Overall, the patterns of infiltration of macrophages and CD8+ T cells were indiscernible between patients with and without dementia, but the co-localization of macrophages and CD8+ T cells along with HIV P24 antigen in the deeper midline and mesial temporal structures of the brain segregated the two groups. This predilection of infected macrophages and CD8+ T cells to the middle part of the brain was unique to both HAD patients, along with unique nature of provirus gag gene sequences derived from macrophages in the midline and mesial temporal structures.
Strong predilection of infected macrophages and CD8+ T cells was typical of the deeper midline and mesial temporal structures uniquely in HAD patients, which has some influence on neurocognitive impairment during HIV infection.
HIV-1 会侵犯中枢神经系统，这对与 HIV 相关的痴呆（HAD）至关重要。但是，细胞浸润和激活与 HIV 一起在 HAD 发展中的作用还了解甚少。
为了研究与 HIV 相关的巨噬细胞和 CD8+T 细胞在有和无痴呆的患者的不同中枢神经系统区域的激活和浸润模式。对两名快速进展性严重痴呆患者的 46 个脑区和 4 名 HIV+非痴呆患者的 53 个脑区进行了分析。使用针对 HIV（P24）、CD8 和 CD68、S-100A8 和颗粒酶 B 抗体的免疫组织化学分析（细胞激活）评估了 HIV 相关的巨噬细胞和 CD8+T 细胞对中枢神经系统的浸润。使用 SPSS 12.0 进行统计分析，采用 Student's t 检验和 ANOVA。
总体而言，有和无痴呆的患者之间巨噬细胞和 CD8+T 细胞的浸润模式难以区分，但 HIV P24 抗原与感染巨噬细胞和 CD8+T 细胞在大脑中线和内侧颞叶结构中的共定位将两组患者区分开来。这种感染巨噬细胞和 CD8+T 细胞向大脑中部的偏好是 HAD 患者所特有的，同时还有从中线和内侧颞叶结构中的巨噬细胞中衍生的前病毒 gag 基因序列的独特性质。
受感染的巨噬细胞和 CD8+T 细胞向中线和内侧颞叶结构深部的强烈偏好是 HAD 患者所特有的，这对 HIV 感染期间的神经认知障碍有一定影响。
