Abstract 13735: CD4+ T-lymphocytes Modulate Wound Healing After Experimental Myocardial Infarction In Mice
Background: Activation and contribution of innate immune cells to myocardial ischemia-reperfusion injury, wound healing and remodelling has been studied in great detail. However, the role of the adaptive immunity, especially T-lymphocytes, has not yet been systematically investigated. Thus, the present study was conducted to evaluate whether CD4+ T-lymphocytes are activated and influence wound healing after myocardial infarction (MI).
Methods and results: Experimental myocardial infarction was induced by permanent ligation of the left coronary artery both in wild-type control (WT) and CD4 knockout mice (CD4 KO) lacking CD4+ T-lymphocytes. Survival and infarct size were not different in WT and CD4 KO mice. Serial echocardiography up to day 56 documented more pronounced left ventricular dilation starting from day 1 post MI in CD4 KO versus WT mice. In CD4 KO animals, the leukocyte infiltrate in the infarct zone on day 7 mainly consisting of CD11b+ neutrophils and monocytes/ macrophages, was significantly greater than in WT mice. As demonstrated by FACS analysis, matrix-metalloproteinase-9 expression was also significantly higher in CD11b+ cells of CD4 KO mice. Moreover, heart-infiltrating monocytes showed significantly higher expression of the inflammatory monocyte marker Ly6C. Angiogenesis and collagen de novo formation were disturbed in myocardial granulation tissue of CD4 KO on day 7. In order to assess whether the mere absence of CD4+ T-cells or lack of antigen recognition by the CD4+ T-cells accounted for the differences between WT and CD4 KO mice, we further studied OT-II mice expressing a transgenic CD4+ T-cell receptor recognizing an ovalbumin-derived peptide. Ventricular remodelling was not different from WT in OT-II mice up to day 56 post MI. However, OT-II mice showed significantly higher mortality and myocardial rupture rate within the first week after MI than did WT mice.
Conclusions: Both, genetic CD4 deficiency (CD4 KO model) and lack of cognate antigen recognition (OT-II model) led to dysfunctional wound healing after MI. Therefore, our study provides first evidence that CD4+ T-cells are activated and, most likely after recognition of cardiac antigens, enhance wound healing following experimental myocardial infarction.
- © 2010 by American Heart Association, Inc.