Vaccination against Foxp3+ regulatory T cells aggravates atherosclerosis

van Es, T.; van Puijvelde, G.H.M.; Foks, A.C.; Habets, K.L.L.; Bot, I.; Gilboa, E.; Van Berkel, T.J.C.; Kuiper, J.

doi:10.1016/j.atherosclerosis.2009.08.041

« Previous Next »Atherosclerosis
Volume 209, Issue 1 , Pages 74-80, March 2010

Vaccination against Foxp3⁺ regulatory T cells aggravates atherosclerosis

T. van Es
- Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands
- These authors contributed equally.
G.H.M. van Puijvelde
- Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands
- These authors contributed equally.
- Corresponding author at: LACDR, Div. of Biopharmaceutics, Gorlaeus Laboratories, Einsteinweg 55, PO Box 9502, 2300 RA Leiden, The Netherlands. Tel.: +31 71 5276051; fax: +31 71 5276032.
A.C. Foks
- Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands
K.L.L. Habets
- Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands
I. Bot
- Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands
E. Gilboa
- Department of Surgery, Duke Center for Translational Research, Durham, NC, United States
T.J.C. Van Berkel
- Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands
J. Kuiper
- Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands

Received 24 July 2009; received in revised form 20 August 2009; accepted 21 August 2009. published online 18 September 2009.

Abstract

Objective

Regulatory T cells are crucial for immune homeostasis and an impaired regulatory T cell function results in many pathological conditions. Regulatory T cells have already been described to be protective in atherosclerosis. However the exact contribution of Foxp3-expressing natural regulatory T cells in atherosclerosis has not been elucidated yet.

Methods and results

In this study we vaccinated LDL receptor deficient mice with dendritic cells which are transfected with Foxp3 encoding mRNA and studied the effect on initial atherosclerosis. Vaccination against Foxp3 resulted in a reduction of Foxp3⁺ regulatory T cells in several organs and in an increase in initial atherosclerotic lesion formation. Furthermore we observed an increase in plaque cellularity and increased T cell proliferation in the Foxp3 vaccinated mice.

Conclusion

We further establish the protective role of Tregs in atherosclerosis. The results illustrate the important role for Foxp3-expressing regulatory T cells in atherosclerosis, thereby providing a potential opportunity for therapeutic intervention against this disease.

Keywords: Atherosclerosis, Inflammation, Vaccination, Regulatory T cells, Foxp3