NDLI: Distinct regulatory roles of transforming growth factor-β and interleukin-4 in the development and maintenance of natural and induced CD4+ CD25+ Foxp3+ regulatory T cells

Content Provider	PubMed Central
Author	Prochazkova, Jana Fric, Jan Katerina, Pokorna Neuwirth, Ales Magdalena, Krulova Zajicova, Alena Holan, Vladimir
Copyright Year	2009
Abstract	The development and function of CD4+ CD25+ Foxp3+ regulatory T cells (Tregs) are strictly regulated by cytokines. Here we show that transforming growth factor-β (TGF-β) and interleukin-4 (IL-4) play a crucial and antagonistic role in the development of Tregs. Additionally, these cytokines also have distinct effects on the maintenance of natural (nTregs) and antigen-induced (iTregs) Tregs. Using double-staining and tracking of proliferation of purified and carboxyflourescein succinimidyl ester (CFSE)-labelled mouse T-cell subpopulations we demonstrated that CD4+ CD25+ Foxp3+ iTregs develop upon alloantigenic stimulation in the presence of TGF-β exclusively from CD4+ CD25− Foxp3− precursors. Both the induction of Foxp3 expression and Treg proliferation were prevented when the cells were stimulated in the presence of IL-4. By contrast, nTregs did not proliferate in the presence of the antigen and TGF-β, and partially lost their Foxp3 expression. IL-4 not only prevented the development of iTregs, but also down-regulated the level of Foxp3 mRNA and decreased the number of Foxp3+ cells in a population of iTregs. Further analyses proved that IL-4 decreased the expression of Foxp3 only in a population of iTregs, whereas it substantially supported the survival of nTregs. Functional experiments showed that Tregs induced in the presence of alloantigen and TGF-β inhibited, on a per-cell basis, cell proliferation comparably to nTregs, and their suppressive capacity was not modulated by IL-4. These data suggest that TGF-β and IL-4 differentially regulate the development of Tregs and distinctly sustain Foxp3 expression and the number of nTregs and iTregs, but have no influence on the suppressive activity of Tregs on a per-cell basis.
Related Links	http://dx.doi.org/10.1111/j.1365-2567.2009.03060.x
Starting Page	670
File Format	PDF
ISSN	13652567
e-ISSN	13652567
Journal	Immunology
Issue Number	1 Pt 2
Volume Number	128
Language	English
Publisher	Blackwell Science Inc
Publisher Date	2009-09-01
Access Restriction	Open
Rights Holder	Blackwell Science Inc
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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