在 HIV 感染期间 PML-IRIS 中 CD8+ T 细胞对 JC 病毒的控制的原位证据。

In situ evidence of JC virus control by CD8+ T cells in PML-IRIS during HIV infection.

机构信息

From the Departments of Infectious and Tropical Diseases (G.M.-B., A.D., P.M., B.M.), Neuroradiology (V.C.), and Pathology (E.U.-C., M.-B.D.), Toulouse University Hospital; INSERM U1043-CNRS UMR 5282 (G.M.-B., L.T.M., R.S.L.), Centre de Physiopathologie Toulouse-Purpan; Université Toulouse III (G.M.-B., V.C., E.U.-C., P.M., M.-B.D., B.M., L.T.M., R.S.L.), France; Center for Brain Research (J.B., H.L.), Medical University of Vienna, Austria; INSERM (E.U.-C., M.-B.D.), CRCT U1087, Toulouse; and CNRS, LCC (B.M.), Université de Toulouse, France.

出版信息

Neurology. 2013 Sep 10;81(11):964-70. doi: 10.1212/WNL.0b013e3182a43e6d. Epub 2013 Aug 9.

DOI:10.1212/WNL.0b013e3182a43e6d

PMID:23935178

Abstract

OBJECTIVE

To determine the pathophysiologic features of progressive multifocal leukoencephalopathy (PML) associated with immune reconstitution inflammatory syndrome (PML-IRIS) in HIV-infected patients.

METHODS

In a cross-sectional study, we retrospectively analyzed 11 HIV-infected patients with a firm diagnosis of PML-IRIS. Brain biopsies were collected from 5 patients and their histopathologic features were compared to those of 4 HIV-infected patients with classic PML.

RESULTS

PML-IRIS developed soon after initiation of antiretroviral therapy in late-presenting HIV-infected patients. The lesions from the 5 biopsied PML-IRIS patients were characterized by a reduction in the density of JC virus (JCV)-infected cells when compared to the 4 patients with PML (11.1 ± 3.2/mm² vs 51.2 ± 4.3/mm², p = 0.01). Comparing the 5 patients with PML-IRIS vs the 4 patients with PML, this correlated with an increased accumulation of CD8+ T cells (818.2 ± 192.8/mm² vs 52.5 ± 10.6/mm², p = 0.01), CD20+ B cells (33.4 ± 13.5/mm² vs 0.5 ± 0.5/mm², p = 0.01), and CD138+ plasma cells (177 ± 84.1/mm² vs 0.25 ± 0.25/mm², p = 0.01), while the number of CD68+ macrophages/microglia did not differ. The ratio between CD8+ T cells and JCV-infected cells was 70 times higher in the 5 patients with PML-IRIS. These findings indicate a clear relationship between an enhanced recruitment of CD8+ T cells and the associated control of the JCV infection.

CONCLUSIONS

Our data provide in situ evidence that PML-IRIS brain lesions are enriched in cytotoxic CD8+ T cells that engage JCV-infected oligodendrocytes. This leads to a better control of JCV dissemination, but at the cost of oligodendrocyte cell death and demyelination.

摘要

目的

确定与 HIV 感染患者免疫重建炎症综合征（PML-IRIS）相关的进行性多灶性白质脑病（PML）的病理生理特征。

方法

在一项横断面研究中，我们回顾性分析了 11 例确诊为 PML-IRIS 的 HIV 感染患者。从 5 例患者中采集了脑活检组织，并将其组织病理学特征与 4 例患有经典 PML 的 HIV 感染患者进行了比较。

结果

在晚期 HIV 感染患者开始接受抗逆转录病毒治疗后不久，PML-IRIS 便出现了。与 4 例 PML 患者相比，5 例 PML-IRIS 患者的活检病变中，JC 病毒（JCV）感染细胞的密度降低（11.1 ± 3.2/mm² vs 51.2 ± 4.3/mm²，p = 0.01）。与 4 例 PML 患者相比，比较这 5 例 PML-IRIS 患者，这与 CD8+T 细胞的积累增加相关（818.2 ± 192.8/mm² vs 52.5 ± 10.6/mm²，p = 0.01），CD20+B 细胞（33.4 ± 13.5/mm² vs 0.5 ± 0.5/mm²，p = 0.01）和 CD138+浆细胞（177 ± 84.1/mm² vs 0.25 ± 0.25/mm²，p = 0.01），而 CD68+巨噬细胞/小胶质细胞的数量没有差异。在 5 例 PML-IRIS 患者中，CD8+T 细胞与 JCV 感染细胞的比值高 70 倍。这些发现表明，CD8+T 细胞的募集增强与 JCV 感染的寡突胶质细胞之间存在明确的关系，从而更好地控制了 JCV 的传播，但代价是少突胶质细胞的死亡和脱髓鞘。