Bcl-2-interacting mediator of cell death influences autoantigen-driven deletion and TCR revision.
J Immunol
; 186(2): 799-806, 2011 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-21148799
ABSTRACT
Peripheral CD4(+)Vß5(+) T cells are tolerized to an endogenous mouse mammary tumor virus superantigen either by deletion or TCR revision. Through TCR revision, RAG reexpression mediates extrathymic TCRß rearrangement and results in a population of postrevision CD4(+)Vß5(-) T cells expressing revised TCRß chains. We have hypothesized that cell death pathways regulate the selection of cells undergoing TCR revision to ensure the safety and utility of the postrevision population. In this study, we investigate the role of Bcl-2-interacting mediator of cell death (Bim)-mediated cell death in autoantigen-driven deletion and TCR revision. Bim deficiency and Bcl-2 overexpression in Vß5 transgenic (Tg) mice both impair peripheral deletion. Vß5 Tg Bim-deficient and Bcl-2 Tg mice exhibit an elevated frequency of CD4(+) T cells expressing both the transgene-encoded Vß5 chain and a revised TCRß chain. We now show that these dual-TCR-expressing cells are TCR revision intermediates and that the population of RAG-expressing, revising CD4(+) T cells is increased in Bim-deficient Vß5 Tg mice. These findings support a role for Bim and Bcl-2 in regulating the balance of survival versus apoptosis in peripheral T cells undergoing RAG-dependent TCR rearrangements during TCR revision, thereby ensuring the utility of the postrevision repertoire.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoantígenos
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Receptores de Antígenos de Linfócitos T
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Linfócitos T CD4-Positivos
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Proteínas Proto-Oncogênicas
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Depleção Linfocítica
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Proteínas Proto-Oncogênicas c-bcl-2
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Proteínas Reguladoras de Apoptose
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Proteínas de Membrana
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos