Regulatory T Lymphocytes Attenuate Myocardial Infarction-Induced Ventricular Remodeling in Mice

Abstract

SummaryDownregulation of CD4+CD25+ regulatory T lymphocytes (Treg) has been found in local atherosclerotic lesions and in patients with myocardial infarction (MI). However, the roles of Treg in MI and the following inflammatory response have not yet been well elucidated. Therefore, we hypothesized that adoptive transfer of Treg could attenuate the postinfarction inflammatory response protecting from adverse remodeling, and we attempted to elucidate the mechanism of delayed heart failure after MI. To clarify the role of Treg in MI, we used a murine MI model and administered a single intravenous injection of Treg (1 × 10 5 ) (treatment, n = 6) or saline (control, n = 7) and sacrificed the mice on day 14. Echocardiograms revealed that Treg improved LV contraction after MI. Histopathology also showed that Treg negated MI-induced LV remodeling. RT-PCR demonstrated that the mRNA levels of IFN-gamma in hearts were lower and Foxp3 in spleens were higher in the treatment group than in the control group. We observed that adoptive Treg transfer could attenuate MI-induced cardiac remodeling through the IFN-gamma and Foxp3 alteration. (Int Heart J 2011; 52: 382-387)

Prognostic Value of Circulating Regulatory T Cells for Worsening Heart Failure in Heart Failure Patients With Reduced Ejection Fraction

“…13) Matsumoto, et al also reported that transfer of Tregs attenuated myocardial infarction-induced ventricular remodelling in mice. 14) These fi ndings suggest that peripheral circulating Tregs might be involved in the pathogenesis of left ventricular dysfunction during development of heart failure.…”

Role of Lymphocytes in Myocardial Injury, Healing, and Remodeling After Myocardial Infarction

“…Accordingly, a single adoptive Treg transfer in a permanent MI mouse model attenuates both the postinfarction inflammatory response and adverse remodeling. 53 However, none of these results define how Tregs exert their beneficial effects. Unanswered questions of particular importance include how therapeutically activated/transferred Tregs interfere with the protective activation of adaptive T-cell immunity as demonstrated in response to MI 20 and how Tregs interact with innate leukocytes.…”

“…53 The mechanism behind these results is not clear, especially because the number of transferred cells only modestly adds to the endogenous Treg pool. Furthermore, most clinical trials of adoptive Treg therapy fail to achieve long-term cell engraftment or substantial clinical benefit, particularly for treating graft versus host disease and type I diabetes mellitus.…”

Immune Cell Modulation of Cardiac Remodeling

“…2,3 However, a role for adaptive immunity responding to damage has also been suspected with protection from MI in animals treated with adoptive transfer of regulatory T cells. 4 Two recent studies show that both dendritic cells (DCs) 5 and T cells 6 are required for proper cardiac remodeling after MI and can play a beneficial role. These 2 studies have remarkably similar phenotypes.…”