Monocytes Prime Autoreactive T cells After Myocardial Infarction.

Monocytes Prime Autoreactive T cells After Myocardial Infarction. Am J Physiol Heart Circ Physiol. 2019 Dec 06;: Authors: DeBerge MP, Yu S, Dehn S, Ifergan I, Yeap XY, Filipp M, Becker A, Luo X, Miller SD, Thorp EB Abstract In humans, loss of central tolerance for the cardiac self-antigen, α-myosin heavy chain (αMyHC), leads to circulation of cardiac autoreactive T cells and renders the heart susceptible to autoimmune attack after acute myocardial infarction (MI). MI triggers profound tissue damage, releasing danger signals and self-antigen by necrotic cardiomyocytes, which leads to recruitment of inflammatory monocytes. We hypothesized that excessive inflammation by monocytes contribute to the initiation of adaptive immune responses to cardiac self-antigen. Using an experimental model of MI in mice, αMHC-mCherry reporter mice, which specifically express mCherry in cardiomyocytes, we detected αMyHC antigen in myeloid cells in the heart-draining mediastinal lymph node (MLN) 7 days after MI. To test whether monocytes were required for cardiac self-antigen trafficking to the MLN, we blocked monocyte recruitment with a CCR2 antagonist or immune modifying nanoparticles (IMP). Blockade of monocyte recruitment reduced αMyHCantigen detection in the MLN after MI. Intramyocardial injection of the model antigen, ovalbumin, into OT-II transgenic mice demonstrated the requirement for monocytes in antigen trafficking and T-cell activation in ...
Source: American Journal of Physiology. Heart and Circulatory Physiology - Category: Physiology Authors: Tags: Am J Physiol Heart Circ Physiol Source Type: research