Generation of autoreactive CD8 T cell in a mouse model of alopecia areata

Abstract Alopecia areata (AA) is the most frequent form of an organ-specific autoimmune disease in humans mediated by NKG2D +CD8 T cells destroying hair follicles. C3H/HeJ mice naturally develop AA similar to humans, and we found it accompanies expansion exhausted phenotype (CD101 +Tim3 +) memory CD8 not only skin skin-draining lymph nodes (SDLNs), but also liver lungs. Before induction, these are activated lungs liver, suggesting they pre-activated organs. In skin, expanded additionally upregulated CD39, PD-1, CTLA-4, which produced less IFNg than those SDLN, when stimulated. These features suggest that autoreactive chronic antigenic stimulation. However, did upregulate TOX, a hallmark cell exhaustion. Intriguingly, CD44 highNKG2D-expressing appeared thymi aged before induction. express TBET EOMES without overt PLZF-expressing cells. Collectively activation explained previously known mechanisms. This research was supported National Research Foundation Korea (NRF-2022R1A2C1007692)