NK cells negatively regulate CD8 T cells via natural cytotoxicity receptor (NCR) 1 during LCMV infection.
PLoS Pathog
; 15(4): e1007725, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30995287
ABSTRACT
Besides their function in recognizing cancerous and virally infected cells, natural killer (NK) cells have the potential to shape adaptive immune responses. However, the mechanisms employed by NK cells to negatively regulate virus-specific CD8 T cell responses remain to be fully defined. Using activating receptor natural cytotoxicity receptor (NCR) 1 deficient (NCR1gfp/gfp) mice, we found increased numbers of virus-specific CD8 T cells, leading to enhanced virus control during acute LCMV infection. Furthermore, virus-specific CD8 T cells were more activated in the absence of NCR1, resulting in exacerbated immunopathology, documented by weight loss, and superior virus control early during chronic LCMV infection. Transfer experiments of virus-specific CD8 T cells into NCR1 deficient hosts revealed a direct cross talk between NK and CD8 T cells. Studies on the splenic microarchitecture revealed pronounced disorganization of T cells in infected NCR1gfp/gfp mice, resulting in enhanced immunopathology and disruption of the T cell niche upon chronic LCMV infection. Our data show a novel pathway employed by NK cells to regulate antiviral CD8 T cell responses, namely direct recognition and elimination of activated CD8 T cells via NCR1 early during infection to protect the host from an overshooting T cell response.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
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Antígenos Ly
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Linfócitos T CD8-Positivos
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Citotoxicidade Imunológica
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Receptor 1 Desencadeador da Citotoxicidade Natural
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Coriomeningite Linfocítica
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Vírus da Coriomeningite Linfocítica
Limite:
Animals
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Suíça