Deep sequencing of the T cell receptor β repertoire reveals signature patterns and clonal drift in atherosclerotic plaques and patients

Abstract

The T cell receptor (TCR) β repertoire directly reflects the status of T cell function. Meanwhile, the immune/inflammatory responses regulated by T cells are the critical determinants of atherosclerosis development. However, due to technical limitations, the composition and molecular characteristics of the TCR repertoire in atherosclerotic patients have not been fully elucidated. In the present study, we use powerful immune repertoire sequencing technology to study this issue. Results show that the utilization of V and/or J genes and the diversity of TCRβ repertoire in atherosclerotic plaques are significantly reduced compared to those in the peripheral blood of normal subjects and atherosclerotic patients. The frequencies of the common T cell clones with certain lengths of the complement determining region 3 regions are notably different among all groups. The high-frequency common clones are also increased in the atherosclerotic plaques compared to that in the other two groups. The expansion of several T cell clonotypes (V29-1J2-1, V20-1J1-6, V6-3J2-7 and V11-2J2-2) is validated in atherosclerotic patients. In short, this study reveals that the diversity of TCR β repertoire significantly decreases in atherosclerotic plaques, probably because of the reduced utilization of VJ genes and marked expansion of some T cell subclones. It provides the basis for understanding the roles of T lymphocytes in the pathogenesis of atherosclerosis.

Myeloid Cell Diversity and Impact of Metabolic Cues during Atherosclerosis

“…This protection was associated with increased IL-10 production, an anti-inflammatory cytokine mainly secreted by regulatory T cells (Tregs). In atherosclerotic patients, an oligoclonal T cell repertoire was observed in comparison to healthy patients [91,92]. This observation further supports the relevance of antigen presentation during disease development.…”

Immunity and Inflammation in Atherosclerosis

“…In addition, T-helper cells show an increasing maturation into antigenexperienced effector/memory (T EM ) and central-memory (T CM ) T cells in the lymph nodes ( Figure 1a) that is also observed in atherosclerotic plaques 28,31 . Sequencing of the TCR revealed an oligoclonal origin of lesional T cells 32,33 suggesting that some (antigenspecific) T cell clones actively expand in the plaque. The enhanced activation of T cells is accompanied by an expansion of lymph nodes draining the atherosclerotic aorta in aged atherosclerotic Apoe −/− mice ( Figure 1b) and a local and systemic pro-inflammatory response that is further enhanced by a hypercholesterolemia-inducing diet [34][35][36] .…”

Comprehensive analysis of T-cell receptor repertoire in patients with acute coronary syndrome by high-throughput sequencing

“…Diversified TCRs were required for an intense adaptive immune responses, while pressures from both internal and external help shape the diversity of TCR [33,34]. The TCR repertoire of patients with atherosclerosis has been investigated and level of diversity was reduced in AS plaques [35]. In the present study, we found that clonal diversity of the TCR CDR3 β decreased in ACS patients as compared to NCA.…”