Abstract:
:Naive CD4 T cells differentiate into functionally distinct T helper (Th) cells subsets or into regulatory T (Treg) cells in response to the cytokine milieu in which they encounter antigen. A recurring theme in post-thymic CD4 T cell differentiation is the cross-regulation of lineage choice by cytokines and transcription factors that are expressed in alternative lineages. For example, TGFbeta induces the de novo expression of the Treg cell signature transcription factor Foxp3, but iTreg differentiation is blocked by high concentrations of the Th2 cytokine IL4. However, whether IL4 can antagonise Foxp3 induction in more physiological settings remains to be addressed. Here we use a co-culture system to demonstrate that IL4 provided by Th2 cells in vitro is sufficient to block Foxp3 induction in naive CD4 T cells. In addition, we find that Foxp3 induction is efficiently blocked not only by the Th2 transcription factor Gata3, but also by PU.1, which is transiently induced during Th2 differentiation. These data suggest that iTreg differentiation may be affected by the polarity of immune responses.
journal_name
Immunol Lettjournal_title
Immunology lettersauthors
Hadjur S,Bruno L,Hertweck A,Cobb BS,Taylor B,Fisher AG,Merkenschlager Mdoi
10.1016/j.imlet.2008.11.001subject
Has Abstractpub_date
2009-01-29 00:00:00pages
37-43issue
1eissn
0165-2478issn
1879-0542pii
S0165-2478(08)00249-6journal_volume
122pub_type
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