Programmed death 1 is highly expressed on CD8+ CD57+ T cells in patients with stable multiple sclerosis and inhibits their cytotoxic response to Epstein-Barr virus.
Immunology
; 152(4): 660-676, 2017 12.
Article
em En
| MEDLINE
| ID: mdl-28767147
ABSTRACT
Growing evidence points to a deregulated response to Epstein-Barr virus (EBV) in the central nervous system of patients with multiple sclerosis (MS) as a possible cause of disease. We have investigated the response of a subpopulation of effector CD8+ T cells to EBV in 36 healthy donors and in 35 patients with MS in active and inactive disease. We have measured the expression of markers of degranulation, the release of cytokines, cytotoxicity and the regulation of effector functions by inhibitory receptors, such as programmed death 1 (PD-1) and human inhibitor receptor immunoglobulin-like transcript 2 (ILT2). We demonstrate that polyfunctional cytotoxic CD8+ CD57+ T cells are able to kill EBV-infected cells in healthy donors. In contrast, an anergic exhaustion-like phenotype of CD8+ CD57+ T cells with high expression of PD-1 was observed in inactive patients with MS compared with active patients with MS or healthy donors. Detection of CD8+ CD57+ T cells in meningeal inflammatory infiltrates from post-mortem MS tissue confirmed the association of this cell phenotype with the disease pathological process. The overall results suggest that ineffective immune control of EBV in patietns with MS during remission may be one factor preceding and enabling the reactivation of the virus in the central nervous system and may cause exacerbation of the disease.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
6_immune_disorders
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6_multiple_sclerosis
Assunto principal:
Regulação da Expressão Gênica
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Herpesvirus Humano 4
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Linfócitos T CD8-Positivos
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Receptor de Morte Celular Programada 1
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Esclerose Múltipla
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Immunology
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Reino Unido