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Unstable atherosclerotic plaques contain T-cells that respond to Chlamydia pneumoniae
O J de Boer1, A C van der Wal, M A Houtkamp
1Department of Cardiovascular Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Insights
Chlamydia pneumoniae infection can activate T cells in atherosclerotic plaques, suggesting a role in chronic inflammation and plaque destabilization in some patients.
Area of Science:
- Immunology
- Cardiovascular Disease
- Infectious Disease
Background:
- Atherosclerosis involves chronic immune inflammation.
- Studies suggest a link between atherosclerosis and Chlamydia pneumoniae infection.
- The role of C. pneumoniae as a causal agent or bystander in atherosclerosis is debated.
Purpose of the Study:
- To investigate the T lymphocyte response to C. pneumoniae within carotid atherosclerotic plaques.
- To determine if C. pneumoniae antigens can activate T cells in the context of atherosclerosis.
Main Methods:
- T cell lines and clones were generated from carotid endarterectomy tissues of symptomatic patients.
- Antigen specificity was assessed using 3H-thymidine incorporation assays against C. pneumoniae elementary bodies.
- Cytokine profiles (Th1/Th2) were determined by measuring IFN-gamma and IL-4 production.
Main Results:
- Five out of eight T-cell lines showed a response to C. pneumoniae.
- Eighteen CD4-positive T cell clones derived from positive cell lines also responded to C. pneumoniae.
- The majority of responsive clones (96%) exhibited a Th1 cytokine profile.
Conclusions:
- C. pneumoniae can activate T cells within atherosclerotic plaques in a subset of symptomatic patients.
- An enhanced pro-inflammatory Th1 response to C. pneumoniae may contribute to plaque destabilization.
- These findings highlight a potential role for C. pneumoniae in the immunopathogenesis of atherosclerosis.
Objective:
Atherosclerotic lesions are characterized by an immune mediated chronic inflammation. Seroepidemiological studies support a relationship between atherosclerotic disease and infection with C. pneumoniae; an association further endorsed by immunocytochemical and DNA directed studies. However, the question arises whether C. pneumoniae acts as a causal antigen, or is merely a bystander. For this reason we have analyzed the T lymphocyte population of carotid atherosclerotic plaques of symptomatic patients for their response against C. pneumoniae.
Methods:
T cell lines were generated from carotid endarterectomy tissues obtained from eight patients with symptomatic disease. The response of these T cell lines against C. pneumoniae elementary bodies was analyzed by 3H-thymidine incorporation. T cell clones were generated by limiting dilution from the cell lines of three patients and tested for antigen specificity in the same manner. Furthermore, cytokine profiles (Th1/Th0/Th2) were established by measuring the production of IFN-gamma and IL-4.
Results:
Of the eight T-cell lines five responded to C. pneumoniae. Eighteen of 69 CD4-positive clones, generated from three patients with a positive T cell lines response, responded to C. pneumoniae also. The majority (17/18, 96%) of these clones showed a Th1 cytokine profile.
Conclusion:
These results show that in a subpopulation of symptomatic patients C. pneumoniae can activate T cells within atherosclerotic plaques suggesting that a C. pneumoniae enhanced proinflammatory Th1 response contributes to plaque destabilization in these patients.