Epstein Barr virus specific T-cells generated from unstable human atherosclerotic lesions: Implications for plaque inflammation.
OBJECTIVE
T-cell activation is an essential feature of atherosclerotic plaque inflammation, which eventually may lead to plaque rupture. In this study, we investigated if EBV, a common herpes virus, is capable of stimulating atherosclerotic plaque derived T-cells and thus could contribute to atherosclerotic plaque inflammation.


METHODS
Plaque derived T-cell cultures were established from symptomatic carotid atherosclerotic plaques of 19 patients. B-cells from the same patients were transformed with EBV to form lymphoblastoid cell lines (B-LCL) that served as antigen presenting cells. The proliferation of T-cells in the presence of autologous B-LCL was analyzed using 3H-thymidine incorporation. The presence of EBV in atherosclerotic material was analyzed by PCR.


RESULTS
Of the 19 cell obtained T-cell cultures, 11 responded to EBV (58%, mean stimulation index: 10.1+/-3.1). PCR analysis showed that EBV DNA was present in 15 of the tissue samples (79%). All the specimens that contained EBV responding T-cells also contained EBV. EBV specific T-cells secreted granzymes, as indication of functional cytotoxic potential.


CONCLUSIONS
EBV-specific cytotoxic T-cells and EBV DNA can be frequently observed in human atherosclerotic plaques. This suggests that a T-cell response against EBV could contribute to plaque inflammation, and thus to the onset of acute clinical symptoms.
de Boer
Onno J
OJ
Department of Pathology, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. o.j.deboer@amc.uva.nl
Teeling
Peter
P
Idu
Mirza M
MM
Becker
Anton E
AE
van der Wal
Allard C
AC
D050197:Atherosclerosis / Q000150:complications / Q000276:immunology* / Q000473:pathology; D002339:Carotid Arteries / Q000473:pathology / Q000821:virology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology*
D004279:DNA, Viral