LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems.
J Clin Invest
; 117(11): 3383-92, 2007 Nov.
Article
em En
| MEDLINE
| ID: mdl-17932562
ABSTRACT
Lymphocyte activation gene-3 (LAG-3) is a cell-surface molecule with diverse biologic effects on T cell function. We recently showed that LAG-3 signaling is important in CD4+ regulatory T cell suppression of autoimmune responses. Here, we demonstrate that LAG-3 maintains tolerance to self and tumor antigens via direct effects on CD8+ T cells using 2 murine systems. Naive CD8+ T cells express low levels of LAG-3, and expression increases upon antigen stimulation. Our data show increased levels of LAG-3 protein on antigen-specific CD8+ T cells within antigen-expressing organs or tumors. In vivo antibody blockade of LAG-3 or genetic ablation of the Lag-3 gene resulted in increased accumulation and effector function of antigen-specific CD8+ T cells within organs and tumors that express their cognate antigen. Most notably, combining LAG-3 blockade with specific antitumor vaccination resulted in a significant increase in activated CD8+ T cells in the tumor and disruption of the tumor parenchyma. A major component of this effect was CD4 independent and required LAG-3 expression by CD8+ T cells. Taken together, these data demonstrate a direct role for LAG-3 on CD8+ T cells and suggest that LAG-3 blockade may be a potential cancer treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antígenos CD
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Subpopulações de Linfócitos T
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Tolerância a Antígenos Próprios
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Linfócitos T CD8-Positivos
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Tolerância Imunológica
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article