Evidence for predilection of macrophage infiltration patterns in the deeper midline and mesial temporal structures of the brain uniquely in patients with HIV-associated dementia

Li Zhou,Carolyn Geczy,Rejane Rua,Yung S Ho,Bruce J Brew,Kenneth Hsu,Thomas Ng,Nitin K Saksena,Valentina Vongrad

doi:10.1186/1471-2334-9-192

Abstract

BackgroundHIV-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.MethodsTo 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.ResultsOverall, 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.ConclusionStrong 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.

Highlights

Human immunodeficiency virus type 1 (HIV-1) penetrates the central nervous system, which is vital for HIV-associated dementia (HAD)
Histopathology and immunohistochemistry Region-specific HIV pathology and cellular-infiltration of macrophages and CD8+ T cells in relation to HIV in the deeper midline and mesial temporal structures is unique to patients with HAD In the 2 rare rapidly progressing dementia patients, the histopathological examination showed severe histopathology typical of HAD[5,6] in most regions (Fig.1)
We first assessed the infiltration of CD68+ macrophages and CD8+ T cells individually, followed by double staining with anti-P24 antibody for topographical tracking and localization of these two cell types in relation to HIV in diverse areas of the CNS from patients with and without dementia

Summary

Introduction

HIV-1 penetrates the central nervous system, which is vital for HIV-associated dementia (HAD). The most popular explanation for this discrepancy is the collapse of immune functions mediated by T cells because cytotoxic T lymphocytes, which are believed to be the principal regulatory elements that control viral production in the periphery and CNS [19,20,21,22,23]. Both CD4+ and CD8+ T lymphocytes have been shown to accumulate in AIDS patients with HIV encephalitis along with the demonstration that brain CD8-CTL are HIV-specific and are associated with HIV encephalitis [24,25,26,27]

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Discussion

Conclusion