Generation of Autoreactive CD8 T Cells in a Mouse Model of Alopecia Areata

This study investigates the role of autoreactive CD8 T cells in alopecia areata (AA) using C3H/HeJ mice, which naturally develop AA similar to humans. The research found that these mice exhibit an expansion of exhausted phenotype memory CD8 T cells in the skin, skin-draining lymph nodes, liver, and lungs. Notably, these CD8 T cells are pre-activated in the lungs and liver before disease induction. In the skin, the CD8 T cells show signs of exhaustion due to chronic antigenic stimulation, although they do not upregulate TOX, a typical marker of T cell exhaustion. Additionally, CD44high NKG2D-expressing CD8 T cells were observed in the thymi of aged mice before disease onset, expressing TBET and EOMES without significant expansion of PLZF-expressing T cells. These findings suggest that AA is mediated by a unique mechanism of autoreactive CD8 T cell activation not previously understood.