Evidence for antigen-driven T-cell response in unstable angina

Background-Activation of T cells and macrophages has been associated with u nstable angina (UA), but whether this reflects specific immune responses re mains unclear. Methods and Results-We analyzed the repertoire and the length of complement arity -determining region 3 of the T cell receptor (TCR) beta-chain variabl e (BV) gene segments of activated lymphocytes in 23 patients with UA, 13 pa tients 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 candid ate 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 signi ficantly higher in UA than in CSA patients. At least one monotypic or oligo typic activated TCRBV population was found in 15 (65%) of 23 UA patients an d in 3 (23%) of 13 CSA patients (P<0.001). Finally, T cells from UA patient s, but not from CSA patients or normal control subjects, proliferated in re sponse to autologous proteins from coronary culprit lesions and/or to oxidi zed LDL. Conclusions-Our findings suggest that the T-cell response observed in UA pa tients is antigen-driven and directed to antigens contained in the culprit coronary atherosclerotic plaques.