Polyclonal origin of T lymphocytes in human atherosclerotic plaques

Abstract

The human atherosclerotic plaque contains large numbers of T lymphocytes and macrophages; this indicates that immune and inflammatory mechanisms may be important factors in the pathogenesis of atherosclerosis. A significant proportion of the T lymphocytes express activation markers, which suggests that they may be stimulated by local antigens, proliferate in response to such antigens, and secrete lymphokines that could serve as paracrine factors in the arterial tissue. However, it is not known, whether plaque T lymphocytes constitute a homogeneous population of clonally proliferating cells or represent a heterogeneous mixture of cells with different immunologic specificities. Clonally-derived T lymphocytes can be identified since they carry identical T cell antigen receptor (TCR) genes. These genes rearrange during T cell ontogeny resulting in TCR genes and TCR proteins that are unique for each T cell clone. We have now employed TCR gene analysis to T lymphocytes derived from atherosclerotic plaques in order to determine their clonal composition. T lymphocytes were isolated from carotid endarterectomy samples and cultured after limiting dilution cell cloning. TCR genes were analyzed by Southern blotting using probes for the TCR gamma (J gamma 2) and TCR beta (C beta 1) genes. TCR gene rearrangement patterns were totally heterogeneous, indicating that plaque T lymphocytes constitute a polyclonal population of cells. This suggests that the T cells are either recruited to the plaque in an activated state or activated locally by mechanisms that do not lead to clonal proliferation.