on September 27, 2007
Published online before print September 27, 2007, doi: 10.1161/ATVBAHA.107.151274
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Submitted on August 26, 2006
Accepted on September 14, 2007
Induction of Oral Tolerance to HSP60 or an HSP60-Peptide Activates T Cell Regulation and Reduces Atherosclerosis
G. H.M. van Puijvelde *;
From the Division of Biopharmaceutics (G.H.M.v.P., T.v.E., E.J.A.v.W., K.L.L.H., P.d.V., T.J.C.v.B., J.K.), Leiden University, and the Department of Infectious Diseases and Immunology (R.v.d.Z., W.v.E.), Utrecht University, the Netherlands
* To whom correspondence should be addressed. E-mail: puijvelde{at}chem.leidenuniv.nl.
Objective—HSP60-specific T cells contribute to the development of the immune responses in atherosclerosis. This can be dampened by regulatory T cells activated via oral tolerance induction, and we explored the effect of oral tolerance induction to HSP60 and the peptide HSP60 (253 to 268) on atherosclerosis.
Methods and Results—HSP60 and HSP60 (253 to 268) were administered orally to LDLr-/- mice before induction of atherosclerosis and resulted in a significant 80% reduction in plaque size in the carotid arteries and in a 27% reduction in plaque size at the aortic root. Reduction in plaque size correlated with an increase in CD4+CD25+Foxp3+ regulatory T cells in several organs and in an increased expression of Foxp3, CD25, and CTLA-4 in atherosclerotic lesions of HSP60-treated mice. The production of interleukin (IL)-10 and transforming growth factor (TGF)-
by lymph node cells in response to HSP60 was observed after tolerance induction.
Conclusion—Oral tolerance induction to HSP60 and a small HSP60-peptide leads to an increase in the number of CD4+CD25+Foxp3+ regulatory T cells, resulting in a decrease in plaque size as a consequence of increased production of IL-10 and TGF-. We conclude that these beneficial results of oral tolerance induction to HSP60 and HSP60 (253 to 268) may provide new therapeutic approaches for the treatment of atherosclerosis.
Key words: atherosclerosis • immune system • tolerance induction • regulatory T cells • heat shock proteins
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