Interleukin-9-secreting CD4 T cells regulate CD8 T cells cytotoxicity in patients with acute coronary syndromes.

T cells play vital roles in the development and progression of acute coronary syndromes (ACS), including cytotoxicity mediated by CD8 T cells and immunoregulatory activity mediated by CD4 T cells. Interleukin (IL)-9-secreting CD4 T cells (Th9 cells) were recently found to be involved in the onset of ACS. We investigated regulatory role of Th9 cells to CD8 T cells in patients with stable angina pectoris, unstable angina pectoris, and acute myocardial infarction (AMI). Circulating Th9 cells percentage, plasma IL-9 level, and PU.1 mRNA relative level was up-regulated in AMI patients compared with controls. There was no significant difference of IL-9-secreting CD8 T cells percentage among groups. CD8 T cells from AMI patients revealed increased cytotoxicity than those from controls, which presented as enhanced cytotolytic activity to target cells, increased interferon-γ and tumor necrosis factor-α secretion, elevated perforin and granzyme B production, and reduced programmed death-1 and cytotoxic T lymphocyte-associated protein 4. IL-9 stimulation did not affect proliferation, but promoted CD8 T-cell cytotoxicity from both controls and AMI patients. IL-9-secreting CD4 T cells were enriched in CD4 CCR4 CCR6 CXCR3 cells. The enhancement of CD8 T-cell cytotoxicity induced by CD4 CCR4 CCR6 CXCR3 cells was dependent on IL-9 secretion. The present results indicated that up-regulation of IL-9-secreting CD4 T cells may contribute to pathogenesis of AMI through enhancement of CD8 T-cell cytotoxicity.