Analysis of the T-cell receptor repertoire in human atherosclerosis

Abstract

The early presence of T-lymphocytes in the atheromatous blood vessel has been interpreted as an indication of specific immunological reactions operating during the course of the atherosclerotic process. Although a T-cell infiltrate characterized by limited usage of TCRAV genes cannot be excluded the unrestricted usage of TCRBV genes argues against a local T-cell clonal expansion in atherogenesis.

The Lymphocytic Infiltration in Calcific Aortic Stenosis Predominantly Consists of Clonally Expanded T Cells

“…Among the possibilities that could account for the conspicuous presence of T cells within CAS valve lesions is that the entrance of T cells is a secondary consequence of chemokines released by valvular injury or non-Ag-specific innate immune system activation of macrophages resulting in a polyclonal T cell infiltration analogous to that of stable atherosclerotic plaques (17)(18)(19)(20). Conversely, if the repertoire consisted of a small number of highly expanded T cell clones, it would favor the interpretation that some features of an adaptive immune response were occurring within the valve perhaps in response to stress-induced molecules, with the potential for the T cell activation and mediator release associated with clonal expansion to enhance valve injury.…”

The Inflammatory Infiltrate in Calcific Aortic Stenosis is Characterized by Clonal Expansions of T Cells and is Associated with Elevated Proportions of Circulating Activated and Effector Memory CD8 T Cells

“…One possibility is that the infiltrating T cells consist of large numbers of unexpanded but clonally different lymphocytes that are recruited as a secondary consequence of attractive chemokines released by events such as valvular injury, atherosclerosis or non-antigen specific innate immune system activation of macrophages. This polyclonal T cell infiltration would be analogous to that found in stable atherosclerotic plaques (Li et al 2005, Oksenberg et al 1997, Stemme et al 1991, Swanson et al 1994. A www.intechopen.com second possibility is that the infiltrating T cells are made up by small numbers of highly expanded T cell clones.…”

“…However, overt unstable atherosclerotic disease was not present in the CAS cases studied by us, suggesting that if the CD4 + CD28 null T cell elevations in the subset of CAS cases with atherosclerotic is mechanistically linked to the atherosclerotic process, the role of this cellular subset in CAS differs from that proposed in unstable atherosclerosis. Moreover, as emphasized by Wu et al (Wu et al 2007), the overall oligoclonal nature and CD8 lineage of valve-infiltrating T cells and those expanded in blood that predominate in CAS contrast sharply with the findings reported in atherosclerosis (Oksenberg et al 1997, Stemme et al 1991. This underlines the fact that the predominant immune mechanism underlying the lymphocytic infiltration in CAS centered on CD8 T cells is distinct from that implicated in atherosclerosis.…”

“…However, the minor proportion of polyclonal, non-expanded T cells in many CAS samples compared to other inflammatory sites such as atherosclerotic plaques of inflamed synovia (Curran et al 2004, Oksenberg et al 1997, Stemme et al 1991, Swanson et al 1994, argues that inflammation-mediated T cell recruitment is not a general feature of CAS.…”

“…Additionally, one instance of a shared, but not detectably expanded, clone between the CD4 blood subset was found (Table 1), in a case that also had atherosclerotic disease. It is possible this instance of a shared T cell clone reflects the contribution of the co-morbid atherosclerotic process (Oksenberg et al 1997, Stemme et al 1991. However, overt unstable atherosclerotic disease was not present in the CAS cases studied by us, suggesting that if the CD4 + CD28 null T cell elevations in the subset of CAS cases with atherosclerotic is mechanistically linked to the atherosclerotic process, the role of this cellular subset in CAS differs from that proposed in unstable atherosclerosis.…”