LAG-3 Confers a Competitive Disadvantage upon Antiviral CD8+ T Cell Responses.
J Immunol
; 197(1): 119-27, 2016 07 01.
Article
em En
| MEDLINE
| ID: mdl-27206765
ABSTRACT
Ongoing clinical trials are evaluating the benefits of systemic blockade of lymphocyte activation gene-3 (LAG-3) signals to improve immunity to tumors. Those studies are founded on the well-established inhibitory role of LAG-3 in regulating CD8(+) T cells during chronic virus infection and antitumor responses. However, the T cell response in LAG-3-deficient mice is similar in size and function to that in wild type animals, suggesting LAG-3 has nuanced immune-regulatory functions. We performed a series of adoptive transfer experiments in mice to better understand the T cell-intrinsic functions of LAG-3 in the regulation of CD8(+) T cell responses. Our results indicate that LAG-3 expression by CD8(+) T cells inhibits their competitive fitness and results in a slightly reduced rate of cell division in comparison with LAG-3-deficient cells. This cell-intrinsic effect of LAG-3 was consistent across both acute and chronic virus infections. These data show that LAG-3 directly modulates the size of the T cell response and support the use of LAG-3 blockade regimens to enhance CD8(+) T cell responses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos CD
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Linfócitos T CD8-Positivos
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Proliferação de Células
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Coriomeningite Linfocítica
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Vírus da Coriomeningite Linfocítica
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2016
Tipo de documento:
Article