Evidence For Antigen-Driven T-Cell Response In Unstable Angina

Background-Activation of T cells and macrophages has been associated with unstable angina (UA), but whether this reflects specific immune responses remains unclear.Methods and Results-We analyzed the repertoire and the length of complementarity -determining region 3 of the T cell receptor (TCR) beta-chain variable (BV) gene segments of activated lymphocytes in 23 patients with UA, 13 patients with chronic stable angina (CSA), and 6 normal control subjects. We also tested the proliferation of systemic T cells in response to autologous coronary plaque proteins, oxidized LDL, and Chlamydia pneumoniae as candidate antigens, in vitro. The activated T cell-TCRBV repertoire was perturbed in 13 (57%) of 23 UA patients versus 3 (23%) of 13 CSA patients (P=0.016) and was restricted to 6 (28%) of 21 expanded TCRBV families; all were significantly higher in UA than in CSA patients. At least one monotypic or oligotypic activated TCRBV population was found in 15 (65%) of 23 UA patients and in 3 (23%) of 13 CSA patients (P<0.001). Finally, T cells from UA patients, but not from CSA patients or normal control subjects, proliferated in response to autologous proteins from coronary culprit lesions and/or to oxidized LDL.Conclusions-Our findings suggest that the T-cell response observed in UA patients is antigen-driven and directed to antigens contained in the culprit coronary atherosclerotic plaques.