Activation of CD4+ T-Lymphocytes Improves Wound Healing and Survival after Experimental Myocardial Infarction in Mice
Background—The role of the adaptive immunity, especially CD4+ T-helper cells, has not yet been systematically investigated in wound healing and remodelling after myocardial infarction (MI). Therefore, we studied, whether CD4+ T-cells become activated and influence wound healing after experimental MI in mice.
Methods and Results—When comparing sham vs. MI in wild-type (WT) mice, T-cell receptor dependent activation of both conventional Foxp3- and regulatory Foxp3+ CD4+ T-cells could be demonstrated in heart-draining lymph nodes within the first week after MI. Concomitantly, we found infiltration of CD4+ T-cells in infarcted myocardium. To study the role of CD4+ T-cells in wound healing and remodelling, CD4+ T-cell deficient mice (CD4 KO, MHCIIΔ/Δ) and T-cell receptor-transgenic OT-II mice recognizing an irrelevant ovalbumin-derived peptide were studied. Serial echocardiography up to day 56 after MI revealed increased left ventricular dilation in CD4 KO when compared to WT mice. Within the infarcted myocardium, CD4 KO mice displayed higher total numbers of leukocytes and of pro-inflammatory monocytes (18.3 ± 3.0 WT vs. 75.7 ± 17.0 CD4 KO, p<0.05). MHCIIΔ/Δ and OT-II mice displayed significantly higher mortality (21% WT vs. 48% OT-II, p<0.05 and WT 22% vs. 52% MHCIIΔ/Δ, p<0.05) and myocardial rupture rates than WT mice. Collagen matrix formation in the infarct zone was severely disturbed in CD4 KO and MHCIIΔ/Δ as well as OT-II mice.
Conclusions—The study provides first evidence that CD4+ T-cells become activated after myocardial infarction, presumably driven by recognition of cardiac autoantigens, and facilitate wound healing of the myocardium.
- Received May 19, 2011.
- Accepted February 6, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited