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Cytokine secretion profiles of cloned T cells from human aortic atherosclerotic plaques
Authors:Onno J. de Boer  Allard C. van der Wal  Claudia E. Verhagen  Anton E. Becker
Abstract:T cells take part in the chronic inflammatory reaction in atherosclerotic plaques, but their specific role in atherosclerosis has not yet been fully elucidated. Nevertheless, one may anticipate that activated T cells may secrete cytokines capable of modulating the morphology and hence the stability of plaques by regulating cell proliferation, lipid metabolism, and extracellular matrix (ECM) synthesis and/or degradation. This study has been designed to investigate the functional properties of T cells in atherosclerotic lesions. For this purpose, T-cell clones were generated from atherosclerotic plaques isolated from human aortas obtained at autopsy from six subjects. Cloned cells were activated with PMA and OKT-3 to initiate cytokine production and cytokine profiles of CD4-positive clones were measured by ELISA. The majority of the T-cell clones (125/155, 81 per cent) produced both interferon (IFN)-γ and interleukin (IL)-4 (type 0 cytokine profile). Moreover, the production of IFN-γ was dominant in the majority of these clones. A type 1 cytokine profile (high levels of IFN-γ and low levels of IL-4) was found in 17 per cent of the clones (27/155). Only three clones (2 per cent) showed a type 2 cytokine secretion pattern (high levels of IL-4 and low levels of IFN-γ). No cytolytic activity could be established in plaque-derived T cells. Our results show that the T-cell population in atherosclerotic lesions is heterogeneous, but the most dominant T cell by far is the one with a type 0 cytokine profile. The dominant secretion of IFN-γ by T-cell clones suggest an important role for plaque T cells in modulating the growth and differentiation of other cells, such as macrophages and smooth muscle cells in atherosclerotic plaques. Copyright © 1999 John Wiley & Sons, Ltd.
Keywords:atherosclerosis  T-cell clones  interferon-γ    interleukin-4  cytokines  Th1 cells  Th0 cells
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