Overexpression of CD6 and PD-1 Identifies Dysfunctional CD8+ T-Cells During Chronic SIV Infection of Rhesus Macaques.
Front Immunol
; 10: 3005, 2019.
Article
em En
| MEDLINE
| ID: mdl-31998302
ABSTRACT
Effective CD8+ T-cell responses play an important role in determining the course of SIV/HIV viral infection. Here we identified a unique population of dysfunctional CD8+ T-cells in lymphoid tissues and bronchoalveolar lavage (BAL) of rhesus macaques with chronic SIV infection characterized by co-expression of CD6 and PD-1. The frequency of CD6 and PD-1 co-expressing CD8+ T-cells was significantly increased in lymphoid tissues and BAL during chronic SIV infection compared to pre-infection levels. These CD6+PD-1+CD8+ T-cells displayed impaired proliferation, cytokine secretion and cytotoxicity compared to their CD6-PD-1+CD8+ T cell counterparts. The frequency of CD8+PD-1+ and CD8+CD6-PD-1+ T-cells in the lymph node and bone marrow did not correlate with SIV viral load, whereas the frequency of CD8+CD6+PD-1+ T-cells positively correlated with SIV viral load in these tissues highlighting the contribution of CD6 to disease progression. CD6+PD-1+CD8+ T-cells expressed elevated levels of SHP2 phosphatase compared to CD6-PD-1+CD8+ T-cells providing a potential mechanism by which CD6 may induce T-cell dysfunction during chronic SIV infection. Combined targeting of CD6 and PD-1 effectively revived the CD8+ T-cell proliferative response in vitro suggesting a strategy for potential therapeutic benefit.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antígenos de Diferenciação de Linfócitos T
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Antígenos CD
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Expressão Gênica
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Síndrome de Imunodeficiência Adquirida dos Símios
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Vírus da Imunodeficiência Símia
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Linfócitos T CD8-Positivos
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Receptor de Morte Celular Programada 1
Limite:
Animals
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos