Cytokine secretion profiles of cloned T cells from human aortic atherosclerotic plaques.
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)-gamma and interleukin (IL)-4 (type 0 cytokine profile). Moreover, 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 per 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 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-gamma 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.
de Boer
O J
OJ
Department of Cardiovascular Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
van der Wal
A C
AC
Verhagen
C E
CE
Becker
A E
AE
D000368:Aged; D001161:Arteriosclerosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D002999:Clone Cells; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D003601:Cytotoxicity Tests, Immunologic; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D016207:Cytokines; D015847:Interleukin-4; D007371:Interferon-gamma