| First Author | Mathes D | Year | 2016 |
| Journal | J Mol Cell Cardiol | Volume | 101 |
| Pages | 99-105 | PubMed ID | 27771254 |
| Mgi Jnum | J:257224 | Mgi Id | MGI:6102122 |
| Doi | 10.1016/j.yjmcc.2016.10.007 | Citation | Mathes D, et al. (2016) CD4(+) Foxp3(+) T-cells contribute to myocardial ischemia-reperfusion injury. J Mol Cell Cardiol 101:99-105 |
| abstractText | OBJECTIVE: The present study analyzed the effect of CD4(+) Forkhead box protein 3 negative (Foxp3(-)) T-cells and Foxp3(+) CD4(+) T-cells on infarct size in a mouse myocardial ischemia-reperfusion model. APPROACH AND RESULTS: We examined the infarct size as a fraction of the area-at-risk as primary study endpoint in mice after 30minutes of coronary ligation followed by 24hours of reperfusion. CD4(+) T-cell deficient MHC-II KO mice showed smaller histologically determined infarct size (34.5+/-4.7% in MHCII KO versus 59.4+/-4.9% in wildtype (WT)) and better preserved ejection fraction determined by magnetic resonance tomography (56.9+/-2.8% in MHC II KO versus 39.0+/-4.2% in WT). MHC-II KO mice also displayed better microvascular perfusion than WT mice after 24hours of reperfusion. Also CD4(+) T-cell sufficient OT-II mice, which express an in this context irrelevant T-cell receptor, revealed smaller infarct sizes compared to WT mice. However, MHC-II blocking anti-I-A/I-E antibody treatment was not able to reduce infarct size indicating that autoantigen recognition is not required for the activation of CD4(+) T-cells during reperfusion. Flow-cytometric analysis also did not detect CD4(+) T-cell activation in heart draining lymph nodes in response to 24hours of ischemia-reperfusion. Adoptive transfer of CD4(+) T-cells in CD4 KO mice increased the infarct size only when including the Foxp3(+) CD25(+) subset. Depletion of CD4(+) Foxp3(+) T-cells in DEREG mice enabling specific conditional ablation of this subset by treatment with diphtheria toxin attenuated infarct size as compared to diphtheria toxin treated WT mice. CONCLUSIONS: CD4(+) Foxp3(+) T-cells enhance myocardial ischemia-reperfusion injury. CD4(+) T-cells exert injurious effects without the need for prior activation by MHC-II restricted autoantigen recognition. |
