Pathogenic CD8+ T cells target K71+ Henle's layer by forming cytolytic immune synapses in Alopecia Areata

CD8+ NKG2D+ T cells mediate hair follicle (HF) damage in Alopecia Areata (AA); however, the mechanisms and targets of T cell attack are not yet known. Here, we showed that CD8+ T cells penetrate the dermal sheath and epithelial layers of HF in AA and stop abruptly upon reaching Henle's layer of the inner root sheath. CD8+ T cells assembled a cytolytic immune synapse (IS) with polarization of Lck kinase and convergence of granzyme B. The formation of IS and localization of caspase-8-dependent apoptosis in KRT71+ Henle's layer of IRS pinpointed these cells as T cell targets in AA. Using direct visualization of in situ activity of pathogenic CD8+ T cells within AA-affected mice skin, we elucidated the molecular mechanism and target of CD8+ T cell cytotoxicity within HF in AA.