CD4 T cell-mediated induction of alopecia areata is dose dependent and requires CD8 T cells

Abstract

Abstract Alopecia Areata (AA) is a common autoimmune disease characterized by infiltration of the hair follicle by T cells, resulting in nonscarring hair loss. Our previous work suggested an increased representation of IFN-γ-producing, activated CD4 T cells in the skin-draining lymph nodes of AA mice when compared to unaffected (UA) controls. Our objective was to determine the contribution of CD4 T cells to AA pathogenesis. We adapted a recently described model of mouse AA induction whereby adoptive transfer of in vitro expanded bulk lymph node (LN) cells from previously affected AA mice induced disease in previously unaffected mice. To address the role CD4 T cells play in AA pathogenesis, we first sorted CD4 T cells and assessed their ability to induce AA. Mouse recipients of in vitro expanded CD4 T cells isolated from the LNs of AA mice developed AA at a substantially increased rate compared to mouse recipients of in vitro-expanded CD4 T cells from LNs of UA mice. CD4-mediated AA induction was found to be dose-dependent, with larger numbers of CD4 T cells inducing disease in recipient mice at a higher rate. Using congenic markers, we found that the transferred CD4 T cells were present in the skin draining LNs of recipient mice at three weeks following transfer but largely absent at 16 weeks, suggesting these cells may be conferring their effect early during disease development. Additionally, we found that the CD4 T cell population is critically dependent on the presence of endogenous CD8 T cells in order to transfer disease. Our data suggests that CD4 T cells are working upstream of CD8 T cells in the pathomechanism of AA. Further studies are needed to dissect how CD4 T cells are enabling CD8 T cell-mediated autoimmune attack on the hair follicle.