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Cardiomyocytes display low mitochondrial priming and are highly resistant toward cytotoxic T‐cell killing
Author(s) -
Zheng Xiang,
Halle Stephan,
Yu Kai,
Mishra Pooja,
Scherr Michaela,
Pietzsch Stefan,
Willenzon Stefanie,
Janssen Anika,
Boelter Jasmin,
HilfikerKleiner Denise,
Eder Matthias,
Förster Reinhold
Publication year - 2016
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201546080
Subject(s) - biology , cytotoxic t cell , priming (agriculture) , mitochondrion , microbiology and biotechnology , genetics , botany , in vitro , germination
Following heart transplantation, alloimmune responses can cause graft rejection by damaging donor vascular and parenchymal cells. However, it remains unclear whether cardiomyocytes are also directly killed by immune cells. Here, we used two‐photon microscopy to investigate how graft‐specific effector CD8 + T cells interact with cardiomyocytes in a mouse heart transplantation model. Surprisingly, we observed that CD8 + T cells are completely impaired in killing cardiomyocytes. Even after virus‐mediated preactivation, antigen‐specific CD8 + T cells largely fail to lyse these cells although both cell types engage in dynamic interactions. Furthermore, we established a two‐photon microscopy‐based assay using intact myocardium to determine the susceptibility of cardiomyocytes to undergo apoptosis. This feature, also known as mitochondrial priming reveals an unexpected weak predisposition of cardiomyocytes to undergo apoptosis in situ. These observations together with the early exhaustion phenotype of graft‐infiltrating specific T cells provide an explanation why cardiomyocytes are largely protected from direct CD8 + T‐cell‐mediated killing.