Beta2-Glycoprotein I is a Target of T Cell Reactivity in Patients with Advanced Carotid Atherosclerotic Plaques

Abstract

Evidence in animal models that beta2-glycoprotein I (beta2GPI), the principal target of autoimmune antiphospholipid antibodies, is involved in the initiation and progression of atherosclerosis, prompted us to investigate the possible role of this self protein as a target autoantigen of immune reactions in patients with carotid atherosclerosis. Plaque-infiltrating T lymphocytes from patients, and circulating T lymphocytes from patients and healthy subjects were tested by cell proliferation assay and by flow cytometry for intracellular cytokine expression in response to beta2GPI. ELISA was used to detect cytokine production in culture supernatants and anti-beta2GPI/anti-cardiolipin antibodies in serum samples. Eight of 35 PBMC samples and 1 of 5 plaque-infiltrating T lymphocyte samples from patients proliferated in response to beta2GPI, whereas PBMC from healthy subjects did not. Patients PBMC samples that proliferated in response to beta2GPI produced significantly higher IFN-gamma and TNF-alpha than non-proliferating PBMC. beta2GPI-specific plaque-derived T lymphocytes expressed IFN-gamma, TNF-alpha and IL-4, suggesting concomitant Th1 and Th2 activation. Only one patients serum was positive for anti-beta2GPI and anti-cardiolipin IgM antibodies. These new findings indicate that beta2GPI induces a cellular immune response in a subpopulation of patients with carotid atherosclerosis thus contributing to the inflammatory responses involved in carotid atherosclerotic disease.