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-β-dependent mechanism. Addition of TGF-β 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-β-dependent manner. Addition of TGF-β 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-β is modulated by the integrated strength of TCR/costimulatory signals.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Gabryšová L,Christensen JR,Wu X,Kissenpfennig A,Malissen B,O'Garra Adoi
10.1002/eji.201041073subject
Has Abstractpub_date
2011-05-01 00:00:00pages
1242-8issue
5eissn
0014-2980issn
1521-4141journal_volume
41pub_type
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