Pro-inflammatory self-reactive T cells are found within murine TCR-αß(+) CD4(-) CD8(-) PD-1(+) cells.
Eur J Immunol
; 46(6): 1383-91, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-27060346
ABSTRACT
TCR-αß(+) double negative (DN) T cells (CD3(+) TCR-αß(+) CD4(-) CD8(-) NK1.1(-) CD49b(-) ) represent a minor heterogeneous population in healthy humans and mice. These cells have been ascribed pro-inflammatory and regulatory capacities and are known to expand during the course of several autoimmune diseases. Importantly, previous studies have shown that self-reactive CD8(+) T cells become DN after activation by self-antigens, suggesting that self-reactive T cells may exist within the DN T-cell population. Here, we demonstrate that programmed cell death 1 (PD-1) expression in unmanipulated mice identifies a subset of DN T cells with expression of activation-associated markers and a phenotype that strongly suggests they are derived from self-reactive CD8(+) cells. We also found that, within DN T cells, the PD-1(+) subset generates the majority of pro-inflammatory cytokines. Finally, using a TCR-activation reporter mouse (Nur77-GFP), we confirmed that in the steady-state PD-1(+) DN T cells engage endogenous antigens in healthy mice. In conclusion, we provide evidence that indicates that the PD-1(+) fraction of DN T cells represents self-reactive cells.
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Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Antígenos CD4
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Autoimunidade
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Subpopulações de Linfócitos T
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Receptores de Antígenos de Linfócitos T alfa-beta
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Antígenos CD8
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Receptor de Morte Celular Programada 1
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article