FOXP3, CBLB and ITCH gene expression and cytotoxic T lymphocyte antigen 4 expression on CD4(+) CD25(high) T cells in multiple sclerosis.
Clin Exp Immunol
; 170(2): 149-55, 2012 Nov.
Article
em En
| MEDLINE
| ID: mdl-23039885
ABSTRACT
Expression of the forkhead box protein 3 (FoxP3) transcription factor is regulated by the E3 ubiquitin ligases Itch and Cbl-b and induces regulatory activity CD4(+) CD25(high) T cells. Treatment with interferon (IFN)-ß enhances regulatory T cell activity in multiple sclerosis (MS). We studied the phenotype of CD4(+) CD25(high) T cells in MS by flow cytometry and its relationship with expression of the FOXP3, ITCH and CBLB genes. We found that untreated MS patients had lower cell surface expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) on CD4(+) CD25(high) T cells and higher intracellular CTLA-4 expression than healthy controls. Cell surface expression of CTLA-4 on CD4(+) CD25(high) T cells correlated with expression of FOXP3 mRNA in untreated patients and increased significantly with time from most recent injection in patients treated with IFN-ß. FOXP3 mRNA expression correlated with CBLB and ITCH and T helper type 2 cytokine mRNA expression in MS patients. These data link expression of FOXP3, CBLB and ITCH mRNA and CTLA-4 expression on the surface of CD4(+) CD25(high) T cell in MS. We hypothesize that this may reflect alterations in the inhibitory effect of CTLA-4 or in regulatory T cell function.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Linfócitos T CD4-Positivos
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Ubiquitina-Proteína Ligases
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas Proto-Oncogênicas c-cbl
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Fatores de Transcrição Forkhead
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Subunidade alfa de Receptor de Interleucina-2
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Antígeno CTLA-4
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Esclerose Múltipla
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article