T_H1 effector CD4 T cells rely on IFN-γ production to induce alopecia areata

Alopecia areata (AA) is an autoimmune disease defined by hair loss and peribulbar infiltrate of CD8 and CD4 T cells. Prior studies have focused on the role of CD8 T cells in the development of AA. Multiple roles for CD4 T cell help have been demonstrated for support of CD8 T cell responses; however, the role of CD4 T cells in AA remains unclear. Here, we demonstrate that CD4 T cells from the skin-draining lymph nodes (SDLNs) of AA mice transferred disease to recipient mice. These cells exhibited a T helper type 1 (T_H1) effector transcriptional and phenotypic profile, and their pathogenic activity required endogenous CD8 T cells and host IFN-γ responsiveness. Targeted deletion of CD4 T cell-mediated production of IFN-γ abrogated the ability of this cell population to transfer disease. Together, these data provide mechanistic insights into pathways driving AA development, strengthening our understanding of the disease and inviting studies into exploring alternative therapeutic strategies for human patients.