Interleukin‐9‐secreting CD4<sup>+</sup> T cells regulate CD8<sup>+</sup> T cells cytotoxicity in patients with acute coronary syndromes
Hongsheng Gang, Dingfeng Peng, Yongjun Hu, Shaoyong Tang, Songhai Li, Qing Huang
Abstract
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.