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Natural regulatory T cells control the development of atherosclerosis in mice

Nature Medicine volume 12, pages 178–180 (2006)Cite this article

Abstract

Atherosclerosis is an immunoinflammatory disease elicited by accumulation of lipids in the artery wall and leads to myocardial infarction and stroke1,2. Here, we show that naturally arising CD4+CD25+ regulatory T cells, which actively maintain immunological tolerance to self and nonself antigens3,4, are powerful inhibitors of atherosclerosis in several mouse models. These results provide new insights into the immunopathogenesis of atherosclerosis and could lead to new therapeutic approaches that involve immune modulation using regulatory T cells.

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Figure 1: Natural regulatory T cells control the development of atherosclerosis.
Figure 2: Partial depletion in CD25+ cells increases lesion size and inflammation in Apoe−/− mice but not in Apoe−/− Cd4-dnTGF-βRII mice.

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References

  1. Binder, C.J. et al. Nat. Med. 8, 1218–1226 (2002).

    Article  CAS  Google Scholar 

  2. Hansson, G.K. N. Engl. J. Med. 352, 1685–1695 (2005).

    Article  CAS  Google Scholar 

  3. Sakaguchi, S. Nat. Immunol. 6, 345–352 (2005).

    Article  CAS  Google Scholar 

  4. von Boehmer, H. Nat. Immunol. 6, 338–344 (2005).

    Article  CAS  Google Scholar 

  5. Daugherty, A. & Rateri, D.L. Circ. Res. 90, 1039–1040 (2002).

    Article  CAS  Google Scholar 

  6. Mallat, Z. et al. Circ. Res. 85, e17–e24 (1999).

    Article  CAS  Google Scholar 

  7. Binder, C.J. et al. J. Clin. Invest. 114, 427–437 (2004).

    Article  CAS  Google Scholar 

  8. King, V.L., Szilvassy, S.J. & Daugherty, A. Arterioscler. Thromb. Vasc. Biol. 22, 456–461 (2002).

    Article  CAS  Google Scholar 

  9. Davenport, P. & Tipping, P.G. Am. J. Pathol. 163, 1117–1125 (2003).

    Article  CAS  Google Scholar 

  10. Mallat, Z. et al. Circulation 108, 1232–1237 (2003).

    Article  CAS  Google Scholar 

  11. Almeida, A.R., Legrand, N., Papiernik, M. & Freitas, A.A. J. Immunol. 169, 4850–4860 (2002).

    Article  Google Scholar 

  12. Salomon, B. et al. Immunity 12, 431–440 (2000).

    Article  CAS  Google Scholar 

  13. Tang, Q. et al. J. Immunol. 171, 3348–3352 (2003).

    Article  CAS  Google Scholar 

  14. Buono, C. et al. Circulation 109, 2009–2015 (2004).

    Article  CAS  Google Scholar 

  15. Robertson, A.K. et al. J. Clin. Invest. 112, 1342–1350 (2003).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Inserm and by Assistance Publique-Hôpitaux de Paris as a Contrat d'Interface (to Z.M.). Inserm U689 and the Center for Molecular Medicine at Karolinska Institute are partners of the European Vascular Genomics Network, a Network of Excellence granted by the European Commission (contract LSHM-CT-2003-503254). We are indebted to B. Levacher and J. Vilard for technical assistance in Q-PCR experiments, to F. Djelti for her technical support and to J. Nemeth for her assistance in the reading of pathological specimens. We are also indebted to L. Chatenoud for providing us with the 2G7 TGF-β–specific antibody and for discussions. H.A.-O. was supported by Fédération Française de Cardiologie.

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale (Inserm), Unit 689, Centre de Recherche Cardiovasculaire Lariboisière, 41, Bd de la Chapelle, Paris, 75010, France

    Hafid Ait-Oufella, Stéphane Potteaux, Joffrey Zoll, Régine Merval, Bruno Esposito, Alain Tedgui & Ziad Mallat

  2. Centre National de la Recherche Scientifique, Unité mixte de Recherche 7087, Groupe Hospitalier Pitié-Salpêtrière, Paris, 75013, France

    Benoît L Salomon, José L Cohen, Sylvain Fisson & David Klatzmann

  3. Department of Medicine, Center for Molecular Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, SE-17176, Sweden

    Anna-Karin L Robertson & Göran K Hansson

  4. Inserm U589, Institut L. Bugnard, Toulouse, 31432, Cedex 4, France

    Pierre Gourdy

  5. Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, 330 Cedar Street, New Haven, 06520, Connecticut, USA

    Richard A Flavell

Authors
  1. Hafid Ait-Oufella
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  2. Benoît L Salomon
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  11. Richard A Flavell
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  12. Göran K Hansson
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  15. Ziad Mallat
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Corresponding author

Correspondence to Ziad Mallat.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Transferred CD4+CD25+ regulatory T cells survive in vivo, retain Foxp3 expression and inhibit proliferation of CD25 deficient cells through Tgf-β and cell-cell contact. (PDF 80 kb)

Supplementary Fig. 2

Transferred CD4+CD25+ regulatory T cells retained high levels of Tgf-β mRNA expression. (PDF 40 kb)

Supplementary Fig. 3

CD4+CD25+ regulatory T cells (Treg) induce a switch toward an anti-inflammatory cytokine profile. (PDF 38 kb)

Supplementary Methods (PDF 42 kb)

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Ait-Oufella, H., Salomon, B., Potteaux, S. et al. Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 12, 178–180 (2006). https://doi.org/10.1038/nm1343

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