Integrated T-cell receptor and costimulatory signals determine TGF-ß-dependent differentiation and maintenance of Foxp3+ regulatory T cells.
Eur J Immunol
; 41(5): 1242-8, 2011 May.
Article
em En
| MEDLINE
| ID: mdl-21469110
ABSTRACT
Foxp3-expressing Tregs play a non-redundant role in protecting against immune pathologies. Foxp3(+) Tregs can arise intra- and extra-thymically, however, the signals directing their differentiation and maintenance in the periphery are not well understood. We show that stimulation of mouse naïve CD4(+) T cells in vitro with optimal doses of anti-CD3/anti-CD28 resulted in high frequencies of Foxp3(+) T cells via a TGF-ß-dependent mechanism. Addition of TGF-ß and retinoic acid overcame the inhibition of Foxp3 expression observed during high-strength anti-CD3/anti-CD28 stimulation. Reducing the strength of TCR or costimulatory signals with inhibitors of mammalian target of rapamycin (mTOR) or MEK/ERK signalling also enhanced expression of Foxp3 in a TGF-ß-dependent manner. Addition of TGF-ß was further required to maintain Foxp3 expression in ex vivo derived Foxp3(+) Tregs upon prolonged anti-CD3/anti-CD28 signalling. Thus, induction/maintenance of Foxp3 expression by TGF-ß is modulated by the integrated strength of TCR/costimulatory signals.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Receptores de Antígenos de Linfócitos T
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Fator de Crescimento Transformador beta
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Linfócitos T Reguladores
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Fatores de Transcrição Forkhead
Limite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Reino Unido