P289	Human C-reactive protein induces dendritic cell-mediated T cell activation.
1E.Van Vre, 1V.Hoymans, 2H.Bult, 3G.Nijs, 1M.Maris, 3D.Van Bockstaele, 1Chr.Vrints, 1J.Bosmans
1University of Antwerp Cardiology, Antwerp, BE; 2University of Antwerp Pharmacology, Antwerp, BE; 3University of Antwerp Hematology, Antwerp, BE.

Background: Dendritic cells (DC) are potent antigen presenting cells that have been implicated in the initiation and progression of atherosclerosis. Serum C-reactive protein (CRP) levels are considered a powerful independent predictor of cardiovascular disease. There is accumulating evidence that CRP also actively contributes to all stages of atherosclerosis, participating in endothelial dysfunction, atherosclerotic plaque formation, plaque maturation, plaque destabilisation and eventually rupture. Recent studies show various pro-atherogenic effects of CRP on different vascular cells. To our knowledge no information exists regarding direct effects of CRP on DC function. Methods: Monocytes from healthy blood donors were differentiated into immature DC and subsequently cultured in the presence of C-reactive protein (100μg/ml). After 24 hours DC morphology and phenotypic changes were examined by respectively light microscopy and flow cytometry. CRP stimulated DC were cocultered with carboxyfluorescein diacetate succinimidyl ester (CFSE) labelled lymphocytes (ratio 1/10, DC/lymphocytes) and T cell proliferation was measured after 8 days. IFNγ secretion by activated T cells was measured by ELISA. Statistical analysis was done with SPSS 12.0. Comparison between the groups was analysed with the Friedman test. Results: DC incubated for 24 hours with 100μg/ml CRP show multiple enlarged cell clusters, and elongated cell morphology when compared with unstimulated control DC. Expression levels of CD80 (p= 0.02, n=5), CD40 (p=0.009, n=5), CD83 (p=0.02, n=5) and CCR7 (p=0.009, n=5) were significantly increased. Expression of HLA-DR and CD86, however, was strong but not different between the (stimulated and unstimulated) groups. After 8 days of coculture T lymphocytes incubated with CRP pulsed DC showed increased proliferation in comparison with the control group (p=0.03, n=3, average increase 53%). In addition IFNγ concentration of the supernatant was significantly increased compared to control supernatant (p=0.02, n=3, average increase 1925pg/ml). Conclusions: CRP induces dendritic cell maturation and dendritic cell-mediated T cell activation. These findings suggest that CRP may induce inflammatory responses, which could contribute to acceleration of atherosclerosis and its complications.

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