Lack of Major Histocompatibility Complex Class I Upregulation and Restrictive Infection by JC Virus Hamper Detection of Neurons by T Lymphocytes in the Central Nervous System.

TitleLack of Major Histocompatibility Complex Class I Upregulation and Restrictive Infection by JC Virus Hamper Detection of Neurons by T Lymphocytes in the Central Nervous System.
Publication TypeJournal Article
Year of Publication2015
AuthorsW├╝thrich, C, Batson, S, Koralnik, IJ
JournalJ Neuropathol Exp Neurol
Volume74
Issue8
Pagination791-803
Date Published2015 Aug
ISSN1554-6578
KeywordsBrain, CD8-Positive T-Lymphocytes, External, Female, Fluorescent Antibody Technique, Histocompatibility Antigens Class I, Humans, JC Virus, Male, Middle Aged, Neurons, Polyomavirus Infections, Up-Regulation
Abstract

The human polyomavirus JC (JCV) infects glial cells in immunosuppressed individuals, leading to progressive multifocal leukoencephalopathy. Polyomavirus JC can also infect neurons in patients with JCV granule cell neuronopathy and JCV encephalopathy. CD8-positive T cells play a crucial role in viral containment and outcome in progressive multifocal leukoencephalopathy, but whether CD8-positive T cells can also recognize JCV-infected neurons is unclear. We used immunohistochemistry to determine the prevalence of T cells in neuron-rich areas of archival brain samples from 77 patients with JCV CNS infections and 94 control subjects. Neurons predominantly sustained a restrictive infection with expression of JCV regulatory protein T antigen (T Ag), whereas glial cells were productively infected and expressed both T Ag and the capsid protein VP1. T cells were more prevalent near JCV-infected cells with intact nuclei expressing both T Ag and VP1 compared with those expressing either protein alone. CD8-positive T cells also colocalized more with JCV-infected glial cells than with JCV-infected neurons. Major histocompatibility complex class I expression was upregulated in JCV-infected areas but could only be detected in rare neurons interspersed with infected glial cells. These results suggest that isolated neurons harboring restrictive JCV infection do not upregulate major histocompatibility complex class I and thus may escape recognition by CD8-positive T cells.

DOI10.1097/NEN.0000000000000218
Alternate JournalJ Neuropathol Exp Neurol
PubMed ID26115192
PubMed Central IDPMC4506730
Grant ListU24 MH100929 / MH / NIMH NIH HHS / United States
U01 MH083500 / MH / NIMH NIH HHS / United States
NS047029 / NS / NINDS NIH HHS / United States
U24 MH100928 / MH / NIMH NIH HHS / United States
R01 NS074995 / NS / NINDS NIH HHS / United States
NS074995 / NS / NINDS NIH HHS / United States
R01 NS047029 / NS / NINDS NIH HHS / United States