Inflammation and TCR signal strength determine the breadth of the T cell response in a bim-dependent manner.
J Immunol
; 192(1): 200-5, 2014 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-24273000
ABSTRACT
Generating a diverse T cell memory population through vaccination is a promising strategy to overcome pathogen epitope variability and tolerance to tumor Ags. The effector and memory pool becomes broad in TCR diversity by recruiting high- and low-affinity T cells. We wanted to determine which factors dictate whether a memory T cell pool has a broad versus focused repertoire. We find that inflammation increases the magnitude of low- and high-affinity T cell responses equally well, arguing against a synergistic effect of TCR and inflammatory signals on T cell expansion. We dissect the differential effects of TCR signal strength and inflammation and demonstrate that they control effector T cell survival in a bim-dependent manner. Importantly, bim-dependent cell death is overcome with a high Ag dose in the context of an inflammatory environment. Our data define the framework for the generation of a broad T cell memory pool to inform future vaccine design.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
/
Transdução de Sinais
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Subpopulações de Linfócitos T
/
Proteínas Proto-Oncogênicas
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Proteínas Reguladoras de Apoptose
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Inflamação
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Proteínas de Membrana
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article