Induction of oral tolerance to HSP60 or an HSP60-peptide activates T cell regulation and reduces atherosclerosis.
Arterioscler Thromb Vasc Biol
; 27(12): 2677-83, 2007 Dec.
Article
em En
| MEDLINE
| ID: mdl-17901374
ABSTRACT
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 ANDRESULTS:
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)-beta by lymph node cells in response to HSP60 was observed after tolerance induction.CONCLUSIONS:
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-beta. 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.
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Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Receptores de LDL
/
Linfócitos T Reguladores
/
Chaperonina 60
/
Aterosclerose
/
Tolerância Imunológica
/
Imunoterapia
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article