Cytokine secretion profiles of cloned T cells from human aortic atherosclerotic plaques

T cells take part in the chronic inflammatory reaction in atherosclerotic p laques, but their specific role in atherosclerosis has not yet been fully e lucidated. Nevertheless, one may anticipate that activated T cells may secr ete cytokines capable of modulating the morphology and hence the stability of plaques by regulating cell proliferation, lipid metabolism, and extracel lular matrix (ECM) synthesis and/or degradation. This study has been design ed to investigate the functional properties of T cells in atherosclerotic l esions. For this purpose, T-cell clones mere 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 product ion and cytokine profiles of CD4-positive clones were measured by ELISA. Th e majority of the T-cell clones (125/155, 81 per cent) produced both interf eron (IFN)-gamma, and interleukin (IL)-4 (type 0 cytokine profile). Moreove r, the production of IFN-gamma was dominant in the majority of these clones . A type 1 cytokine profile (high levels of IFN-gamma and low levels of IL- 4) was found in 17 per cent of the clones (27/155). Only three clones (2 pe r cent) showed a type 2 cytokine secretion pattern (high levels of IL-4 and low levels of IFN-gamma). No cytolytic activity could be established in pl aque-derived T cells. Our results show that the T-cell population in athero sclerotic 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-gamma by T-cell clones suggest an important role for plaque T cells in modulatin g the growth and differentiation of other cells, such as macrophages and sm ooth muscle cells in atherosclerotic plaques. Copyright (C) 1999 John Wiley & Sons, Ltd.