Cutting edge: Lymphoproliferation caused by Fas deficiency is dependent on the transcription factor eomesodermin.
J Immunol
; 185(12): 7151-5, 2010 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-21076068
ABSTRACT
A hallmark of autoimmune lymphoproliferative syndrome (ALPS), caused by mutation of the Fas death receptor, is massive lymphadenopathy from aberrant expansion of CD4(-)CD8(-) (double-negative [DN]) T cells. Eomesodermin (Eomes) is a member of the T-box family of transcription factors and plays critical roles in effector cell function and memory cell fitness of CD8(+) T lymphocytes. We provide evidence in this study that DN T cells exhibit dysregulated expression of Eomes in humans and mice with ALPS. We also find that T cell-specific deletion of Eomes prevents lymphoid hypertrophy and accumulation of DN T cells in Fas-mutant mice. Although Eomes has critical physiological roles in the function and homeostasis of CD8(+) T cells, overexpression of Eomes appears to enable pathological induction or expansion of unusual CD8-related T cell subsets. Thus, antagonism of Eomes emerges as a therapeutic target for DN T cell ablation in ALPS.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Subpopulações de Linfócitos T
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Linfócitos T CD8-Positivos
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Receptor fas
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Proteínas com Domínio T
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Síndrome Linfoproliferativa Autoimune
Tipo de estudo:
Clinical_trials
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2010
Tipo de documento:
Article