The damage of myocardial infarction (MI) is often progressive. A possible mechanism for subsequent myocardial damage and heart failure after MI is immune response against cardiac self-antigens. The purpose of our study was to test the hypothesis that cytotoxic T lymphocytes are activated following acute MI and may have a role in producing further myocardial damage. Rats were allocated into three experimental groups: acute MI, Sham MI and non-operated control. One, two and three weeks after surgery, lymphocytes were obtained from rat spleens and incubated with neonatal cardiac myocytes. Lymphocyte proliferation was assessed by a thymidine incorporation assay and calculated as proliferation index (PI). Myocyte destruction was measured by a crystal-violet staining assay and expressed as percentage of cell destruction. Proliferation index was significantly higher among lymphocytes obtained from MI animals (44.3 ± 5.8 and 44.9 ± 5.1, at 2 and 3 weeks after MI. respectively) than sham MI (29.3 ± 5.3, 27.1 ± 4.7) (P<0.05) or control animals (17.1 ± 2.5, 16.2 ± 2.8) (P = 0.03). Cytotoxic activity of the MI lymphocytes against the cultured cardiomyocytes was significantly 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 ± 5.4%, 17.4 ± 6.1%) (P<0.001). The cytotoxic 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 pathophysiological insights may provide novel oportunities to prevent death of non-ischemic cardiomyocytes and heart failure following myocardial infarction.
Bibliographical noteFunding Information:
This work was supported by the Tiber and Slezak funds of Tel-Aviv University.
- Myocardial infarction