Publikation
Myocardial Infarction Primes Autoreactive T Cells through Activation of Dendritic Cells
Wissenschaftlicher Artikel/Review - 21.03.2017
Van der Borght Katrien, Carmeliet Peter, Guilliams Martin, Gillebert Thierry, Ludewig Burkhard, Saeys Yvan, De Prijck Sofie, Vanheerswynghels Manon, Van Moorleghem Justine, Sichien Dorine, Martens Liesbet, Bouché Ann, Nindl Veronika, Scott Charlotte L, Lambrecht Bart N
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Peripheral tolerance is crucial for avoiding activation of self-reactive T cells to tissue-restricted antigens. Sterile tissue injury can break peripheral tolerance, but it is unclear how autoreactive T cells get activated in response to self. An example of a sterile injury is myocardial infarction (MI). We hypothesized that tissue necrosis is an activator of dendritic cells (DCs), which control tolerance to self-antigens. DC subsets of a murine healthy heart consisted of IRF8-dependent conventional (c)DC1, IRF4-dependent cDC2, and monocyte-derived DCs. In steady state, cardiac self-antigen α-myosin was presented in the heart-draining mediastinal lymph node (mLN) by cDC1s, driving the proliferation of antigen-specific CD4(+) TCR-M T cells and their differentiation into regulatory cells (Tregs). Following MI, all DC subsets infiltrated the heart, whereas only cDCs migrated to the mLN. Here, cDC2s induced TCR-M proliferation and differentiation into interleukin-(IL)-17/interferon-(IFN)γ-producing effector cells. Thus, cardiac-specific autoreactive T cells get activated by mature DCs following myocardial infarction.