Editors' ChoiceInflammation

T Cells in Healing Infarcts

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Science Translational Medicine  28 Mar 2012:
Vol. 4, Issue 127, pp. 127ec54
DOI: 10.1126/scitranslmed.3004037

Today, ~90% of patients survive an acute infarct. However, many survivors do not beat the clock; in other words, the “time is muscle” paradigm—which implies that ischemic myocardium can be salvaged if reperfused quickly—works against them. Dying cardiac tissue also triggers a biologically universal wound-healing program that is dominated by innate immune cells. Conversely, Hofmann et al. highlight the role of the adaptive (versus innate) arm of the immune system: specifically, how T cells may regulate repair of the damaged heart.

The authors noted conventional and regulatory Foxp3+ CD4+ T cells in infarcted mouse hearts after coronary ligation. Although the frequency of T cells in the infarct remained low at <1% of all cells, they appeared to have an outsized role in orchestrating wound healing. In CD4+ T cell–deficient mice, inflammatory Ly-6Chigh monocytes lingered longer in the infarct than in mice with T cells. The impaired resolution of inflammation disturbed collagen matrix formation, caused higher ventricular rupture rates, and enhanced dilation of the left ventricle. Experiments in transgenic mice with a dysfunctional T cell receptor suggested that antigen presentation was involved in the observed T cell activation; however, it is unclear at this point which cells presented what antigen.

Innate immune cells are typically central to wound healing, especially neutrophils, monocytes, and macrophages. The study by Hofmann and colleagues further blurs the lines separating innate and adaptive immunity. T cells may regulate innate immune cell activity in infarct healing. If an infarct heals well, a small and strong scar preserves the ventricle’s integrity; if not, the infarct expands, which initiates progressive chamber dilation, leading to heart failure. Studies like the one from Hofmann et al. bring us closer to harnessing this process as a therapeutic opportunity.

U. Hofmann et al., Activation of CD4+ T-lymphocytes improves wound healing and survival after experimental myocardial infarction in mice. Circulation 2 March 2012 (10.1161/CIRCULATIONAHA.111.044164). [Abstract]

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