In situ evidence of JC virus control by CD8+ T cells in PML-IRIS during HIV infection
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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.
GLOSSARY
- 1H MRS=
- proton magnetic resonance spectroscopy;
- HAART=
- highly active antiretroviral therapy;
- IRIS=
- immune reconstitution inflammatory syndrome;
- JCV=
- JC virus;
- MHC=
- major histocompatibility complex;
- MS=
- multiple sclerosis;
- PML=
- progressive multifocal leukoencephalopathy;
- SV40=
- simian virus 40
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Supplemental data at www.neurology.org
- Received March 10, 2013.
- Accepted in final form June 4, 2013.
- © 2013 American Academy of Neurology
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