Activation of CD4+ T Lymphocytes Improves Wound Healing and Survival After Experimental Myocardial Infarction in Mice

U Hofmann, N Beyersdorf, J Weirather, A Podolskaya… - Circulation, 2012 - Am Heart Assoc
U Hofmann, N Beyersdorf, J Weirather, A Podolskaya, J Bauersachs, G Ertl, T Kerkau…
Circulation, 2012Am Heart Assoc
Background—The role of adaptive immunity, especially CD4+ T-helper cells, has not yet
been systematically investigated in wound healing and remodeling 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 we compared
sham versus 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 …
Background
The role of adaptive immunity, especially CD4+ T-helper cells, has not yet been systematically investigated in wound healing and remodeling 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 we compared sham versus 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 remodeling, CD4+ T-cell–deficient mice (CD4 knockout [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 compared with WT mice. Within the infarcted myocardium, CD4 KO mice displayed higher total numbers of leukocytes and proinflammatory monocytes (18.3±3.0 104/mg WT versus 75.7±17.0 104/mg CD4 KO, P<0.05). MHCIIΔ/Δ and OT-II mice displayed significantly greater mortality (21% WT versus 48% OT-II, P<0.05, and WT 22% versus 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 mice, as well as in OT-II mice.
Conclusions
The present study provides the first evidence that CD4+ T cells become activated after MI, presumably driven by recognition of cardiac autoantigens, and facilitate wound healing of the myocardium.
Am Heart Assoc