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A functional role for inducible costimulator (ICOS) in atherosclerosis
- Source :
- Atherosclerosis. 183:57-63
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- Background: Lymphocytes appear to influence atherosclerosis by altering cytokine production. Whereas primary lymphocyte activation requires T cell receptor ligation, costimulatory signals also appear requisite for generation of a functional T cell response. Inducible costimulator (ICOS) is a newly discovered T cell molecule with a dual role in immune mediated disorders. Herein, we tested the importance of ICOS in atherosclerosis. Methods and results: Atherosclerotic plaques from ApoE-KO mice were studied immunohistochemically for the presence and localization of ICOS and its receptors and its expression in splenocytes. ApoE-KO mice were immunized with human ICOS/Fc-chimera or non-fused Fc and either provided a chow diet for 6 weeks, or a high fat diet for 8 weeks. ICOS and its ligand were abundantly expressed within plaques from ApoE-KO mice: Spleen cells from atherosclerotic mice exhibited lowered constitutive expression of ICOS yet priming with oxLDL enhanced ICOS expression dose-dependently. In mice induced to develop fatty streaks and to generate ICOS blocking antibodies, early atherosclerosis was increased by ∼77% whereas upon inducing more advanced lesions, the increase in plaque area upon ICOS blockade group was ∼36%. IFN-gamma secretion by oxLDL-primed splenocytes in ICOS-immunized mice increased whereas IL-10 secretion diminished as compared to control animals. A similar trend in cytokine production was evident in the lesion by immunohistochemistry. Conclusion: ICOS appears as an influential costimulatory pathway in atherosclerosis that may play a protective rather that a proatherogenic role.
- Subjects :
- Antigens, Differentiation, T-Lymphocyte
Recombinant Fusion Proteins
T-Lymphocytes
medicine.medical_treatment
T cell
Lymphocyte
Aortic Diseases
Biology
Lymphocyte Activation
Hyperlipoproteinemia Type II
Inducible T-Cell Co-Stimulator Protein
Interferon-gamma
Mice
Apolipoproteins E
Immune system
Isoantibodies
medicine
Animals
Humans
Receptor
Aorta
Autoantibodies
Mice, Knockout
T-cell receptor
Atherosclerosis
Immunoglobulin Fc Fragments
Interleukin-10
Lipoproteins, LDL
Mice, Inbred C57BL
Interleukin 10
Cytokine
medicine.anatomical_structure
Immunology
Diet, Atherogenic
Immunization
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 00219150
- Volume :
- 183
- Database :
- OpenAIRE
- Journal :
- Atherosclerosis
- Accession number :
- edsair.doi.dedup.....eb0d9d1e34cdc280311933329437faea