The Journal of Experimental Medicine
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Published 21 July 2003. doi:10.1084/jem.20030654
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© Rockefeller University Press, 0022-1007/2003/7/259 $5.00
The Journal of Experimental Medicine, Volume 198, Number 2, 259-266

CD4+ CD25+ Regulatory T Cells Control T Helper Cell Type 1 Responses to Foreign Antigens Induced by Mature Dendritic Cells In Vivo

Guillaume Oldenhove1, Magali de Heusch1, Georgette Urbain-Vansanten1, Jacques Urbain1, Charlie Maliszewski2, Oberdan Leo1 and Muriel Moser1

1 Institut de Biologie et Médecine Moléculaires, Université Libre de Bruxelles, 6041 Gosselies, Belgium
2 Amgen Corporation, Seattle, WA 98101

Address correspondence to Muriel Moser, Laboratoire de Physiologie Animale, Université Libre de Bruxelles, Rue des Prof. Jeener et Brachet, 12, 6041 Gosselies, Belgium. Phone: 32-2-650-98-63; Fax: 32-2-650-98-60; E-mail: mmoser{at}ulb.ac.be

Recent evidence suggests that in addition to their well known stimulatory properties, dendritic cells (DCs) may play a major role in peripheral tolerance. It is still unclear whether a distinct subtype or activation status of DC exists that promotes the differentiation of suppressor rather than effector T cells from naive precursors. In this work, we tested whether the naturally occurring CD4+ CD25+ regulatory T cells (Treg) may control immune responses induced by DCs in vivo. We characterized the immune response induced by adoptive transfer of antigen-pulsed mature DCs into mice depleted or not of CD25+ cells. We found that the development of major histocompatibility complex class I and II–restricted interferon {gamma}–producing cells was consistently enhanced in the absence of Treg. By contrast, T helper cell (Th)2 priming was down-regulated in the same conditions. This regulation was independent of interleukin 10 production by DCs. Of note, splenic DCs incubated in vitro with Toll-like receptor ligands (lipopolysaccharide or CpG) activated immune responses that remained sensitive to Treg function. Our data further show that mature DCs induced higher cytotoxic activity in CD25-depleted recipients as compared with untreated hosts. We conclude that Treg naturally exert a negative feedback mechanism on Th1-type responses induced by mature DCs in vivo.

Key Words: primary response • T helper cell type 1/type 2 balance • regulation • inflammation • Toll-like receptors


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