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)‐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.

[1]  A. Becker,et al.  Leucocyte recruitment in rupture prone regions of lipid-rich plaques: a prominent role for neovascularization? , 1999, Cardiovascular research.

[2]  A. O’Garra,et al.  Cytokines induce the development of functionally heterogeneous T helper cell subsets. , 1998, Immunity.

[3]  C E Verhagen,et al.  Type 1- and type 2-like lesional skin-derived Mycobacterium leprae-responsive T cell clones are characterized by coexpression of IFN-gamma/TNF-alpha and IL-4/IL-5/IL-13, respectively. , 1998, Journal of immunology.

[4]  L Adorini,et al.  The interleukin-12/interleukin-12-receptor system: role in normal and pathologic immune responses. , 1998, Annual review of immunology.

[5]  Kenneth M. Murphy,et al.  Functional diversity of helper T lymphocytes , 1996, Nature.

[6]  S. Romagnani.  Th1 and Th2 in human diseases. , 1996, Clinical immunology and immunopathology.

[7]  M L Woods,et al.  Increased incidence of Chlamydia species within the coronary arteries of patients with symptomatic atherosclerotic versus other forms of cardiovascular disease. , 1996, Journal of the American College of Cardiology.

[8]  B. McManus,et al.  Human transplant coronary artery disease: pathological evidence for Fas-mediated apoptotic cytotoxicity in allograft arteriopathy. , 1996, Laboratory investigation; a journal of technical methods and pathology.

[9]  L. Demer,et al.  Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis. , 1996, The Journal of clinical investigation.

[10]  C. Alpers,et al.  Neovascular expression of E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 in human atherosclerosis and their relation to intimal leukocyte content. , 1996, Circulation.

[11]  J. Frostegård,et al.  Oxidized LDL induces enhanced antibody formation and MHC class II-dependent IFN-gamma production in lymphocytes from healthy individuals. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[12]  J. Witztum,et al.  T lymphocytes from human atherosclerotic plaques recognize oxidized low density lipoprotein. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Dayer,et al.  Immobilized anti-CD3 antibody activates T cell clones to induce the production of interstitial collagenase, but not tissue inhibitor of metalloproteinases, in monocytic THP-1 cells and dermal fibroblasts. , 1995, Journal of immunology.

[14]  P. Libby,et al.  Enhanced Expression of Vascular Matrix Metalloproteinases Induced In Vitro by Cytokines and in Regions of Human Atherosclerotic Lesions a , 1994, Annals of the New York Academy of Sciences.

[15]  P. Libby,et al.  Regulation of smooth muscle cell scavenger receptor expression in vivo by atherogenic diets and in vitro by cytokines. , 1995, The Journal of clinical investigation.

[16]  P. Libby,et al.  Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. , 1994, Circulation research.

[17]  A. Becker,et al.  Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. , 1994, Circulation.

[18]  Qingbo Xu,et al.  Immunology of atherosclerosis. Demonstration of heat shock protein 60 expression and T lymphocytes bearing alpha/beta or gamma/delta receptor in human atherosclerotic lesions. , 1993, The American journal of pathology.

[19]  A. Becker,et al.  Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions. , 1992, The American journal of pathology.

[20]  G. Hansson,et al.  Interferon-gamma inhibits scavenger receptor expression and foam cell formation in human monocyte-derived macrophages. , 1992, The Journal of clinical investigation.

[21]  P. Libby,et al.  Atherogenic diets enhance endotoxin-stimulated interleukin-1 and tumor necrosis factor gene expression in rabbit aortae. , 1992, The Journal of nutrition.

[22]  P. Libby,et al.  Cytokines and growth factors positively and negatively regulate interstitial collagen gene expression in human vascular smooth muscle cells. , 1991, Arteriosclerosis and thrombosis : a journal of vascular biology.

[23]  H. Rus,et al.  Tumor necrosis factor-alpha in human arterial wall with atherosclerosis. , 1991, Atherosclerosis.

[24]  M. Piccinni,et al.  Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[25]  M. Fishbein,et al.  Tumor necrosis factor gene expression in human vascular intimal smooth muscle cells detected by in situ hybridization. , 1990, The American journal of pathology.

[26]  G. Hansson,et al.  MHC class II antigen expression in human vascular smooth muscle cells is induced by interferon-gamma and modulated by tumour necrosis factor and lymphotoxin. , 1990, Immunology.

[27]  G. Gabbiani,et al.  Interferon gamma inhibits both proliferation and expression of differentiation-specific alpha-smooth muscle actin in arterial smooth muscle cells , 1989, The Journal of experimental medicine.

[28]  A. Becker,et al.  Atherosclerotic lesions in humans. In situ immunophenotypic analysis suggesting an immune mediated response. , 1989, Laboratory investigation; a journal of technical methods and pathology.

[29]  G. Hansson,et al.  Detection of activated T lymphocytes in the human atherosclerotic plaque. , 1989, The American journal of pathology.

[30]  A. Clowes,et al.  Gamma-interferon regulates vascular smooth muscle proliferation and Ia antigen expression in vivo and in vitro. , 1988, Circulation research.

[31]  G. Gabbiani,et al.  Expression of class II transplantation antigen on vascular smooth muscle cells in human atherosclerosis. , 1985, The Journal of clinical investigation.