Abstract 12010: Role of T-cells in Myocardial Ischemia-Reperfusion Injury
Background: Leukocytes, especially neutrophils, contribute to myocardial ischemia-reperfusion injury. We could recently demonstrate that myocardial wound healing is facilitated by CD4+ T-cells. We therefore studied the role of T-cells during ischemia-reperfusion of the myocardium.
Methods and Results: Leukocyte infiltration was determined by FACS analysis and immunohistology after experimental ischemia-reperfusion in mice. Significantly more CD3+ T-cells infiltrated the mouse myocardium after 30 minutes of ischemia and 24 hours of reperfusion in comparison to sham operated mice. CD4+ T-cells (47%) and CD8+ T-cells (30%) were the predominant T-cell subsets among all CD45+CD3+ leukocytes recruited to the myocardium during reperfusion. NK T-cells and γδ T-cells could also be detected in reperfused myocardium. Evans Blue/ TTC-staining demonstrated that CD4 KO (which lack CD4+ T-cells), OTII T-cell receptor transgenic mice (which have a high specificity for ovalbumin derived peptides) but not CD8 KO (which lack CD8+ T-cells) mice each showed significantly reduced infarct size in comparison to WT mice (area at risk/ infarct size: WT 67% vs. CD4 KO 48%, OTII 34% p<0.05, CD8 KO 66%). The reduction in infarct size in OTII mice and the observed upregulation of CD40L in response to ischemia-reperfusion on CD4+ T-cells indicates that antigen recognition and subsequent activation might play a role for the detrimental effect of CD4+ T-cells on the ischemia-reperfusion injury. In OTII and CD4 KO mice the absolute number of neutrophils within the area at risk was less than in WT mice.
Conclusions: CD4+, but not CD8+ T-cells, contribute to myocardial ischemia-reperfusion injury, obviously after recognition of self-antigens.
- © 2012 by American Heart Association, Inc.