Cytotoxic T lymphocytes are activated following myocardial infarction and can recognize and kill healthy myocytes in vitro

The damage of myocardial infarction (MI) is often progressive. A possible m echanism for subsequent myocardial damage and heart failure after MI is imm une response against cardiac self-antigens. The purpose of our study was to test the hypothesis that cytotoxic T lymphocytes are activated following a cute MI and may have a role in producing further myocardial damage. Rats we re allocated into three experimental groups: acute MI, Sham MI and non-oper ated control. One, two and three weeks after surgery, lymphocytes were obta ined from rat spleens and incubated with neonatal cardiac myocytes. Lymphoc yte proliferation was assessed by a thymidine incorporation assay and calcu lated as proliferation index (PI). Myocyte destruction was measured by a cr ystal-violet staining assay and expressed as percentage of cell destruction . Proliferation index was significantly higher among lymphocytes obtained f rom MI animals (44.3 +/- 5.8 and 44.9 +/- 5.1, at 2 and 3 weeks after MI, r espectively) than sham MT (29.3 +/- 5.3, 27.1 +/- 4.7) (P < 0.05) or contro l animals (17.1 <plus/minus> 2.5, 16.2 +/- 2.8) (P = 0.03). Cytotoxic activ ity of the MI lymphocytes against the cultured cardiomyocytes was significa ntly higher 2 and 3 weeks after MI, (36.4 +/- 7.3%, 69.3 +/- 4.9%) compared to sham MI (17.9 +/- 3.14%, 36.6 +/- 5.3%) (P < 0.001) and control animals respectively (13.3 <plus/minus> 5.4%, 17.4 +/- 6.1%) (P < 0.001). The cyto toxic activity against healthy cardiomyocytes was myocyte specific, induced by CD8 lymphocytes and major-histocompatibility complex (MHC) restricted. Cytotoxic T lymphocytes (CD8) are activated following MI and can recognize and kill normal cardiomyocytes in vitro. The newly described pathophysiolog ical insights may provide novel opportunities to prevent death of non-ische mic cardiomyocytes and heart failure following myocardial infarction. (C) 2 000 Academic Press.