A virtual memory CD8+ T cell-originated subset causes alopecia areata through innate-like cytotoxicity
Authors
Joon Seok ; Sung-Dong Cho ; Jeongsoo Lee ; Yunseo Choi ; Su-Young Kim ; Sung-Min Lee ; Sang-Hoon Kim ; Seongju Jeong ; Minwoo Jeon ; Hoyoung Lee ; A Reum Kim ; Baekgyu Choi ; Sang-Jun Ha ; Inkyung Jung ; Ki-Jun Yoon ; Jong-Eun Park ; Jong Hoon Kim ; Beom Joon Kim ; Eui-Cheol Shin ; Su-Hyung Park
Virtual memory T (TVM) cells are a T cell subtype with a memory phenotype but no prior exposure to foreign antigen. Although TVM cells have antiviral and antibacterial functions, whether these cells can be pathogenic effectors of inflammatory disease is unclear. Here we identified a TVM cell-originated CD44super-high(s-hi)CD49dlo CD8+ T cell subset with features of tissue residency. These cells are transcriptionally, phenotypically and functionally distinct from conventional CD8+ TVM cells and can cause alopecia areata. Mechanistically, CD44s-hiCD49dlo CD8+ T cells could be induced from conventional TVM cells by interleukin (IL)-12, IL-15 and IL-18 stimulation. Pathogenic activity of CD44s-hiCD49dlo CD8+ T cells was mediated by NKG2D-dependent innate-like cytotoxicity, which was further augmented by IL-15 stimulation and triggered disease onset. Collectively, these data suggest an immunological mechanism through which TVM cells can cause chronic inflammatory disease by innate-like cytotoxicity.