Treatment With Cd122 Antibody Durably Reverses Autoirnmune Skin Disease In A Mouse Model Of Vitiligo

Vitiligo is a disfiguring autoimmune skin disease characterized by patchy depigmentation. Vitiligo affects approximately 1% of the population worldwide, and it is mediated by CD8+ T cells that kill melanocytes, the pigment producing cells in the skin. Like many autoimmune diseases, treatment options for vitiligo are limited, and depigmentation rapidly recurs after therapy is stopped. We hypothesized that tissue resident memory T cells (Trm) persisted in the skin to reactivate disease. We first confirmed the presence of melanocyte-specific cells with Trm phenotypes in biopsies from human patients and in a mouse model of vitiligo. Functional analysis of Trm cells in mice with vitiligo revealed that they can sense antigen in the skin as determined by Nur77-GFP reporting, as well as secrete cytokines and chemokines as determined by IFNγ, CXCL9 and CXCL10 reporting. Treatment with the S1P 1 inhibitor FTY720 resulted in rapid repigmentation, yet preserved Trm. Treatment with a CD122 blocking antibody effectively depleted autoreactive Trm. Importantly, CD122 antibody was also able to durably reverse disease mice. We propose that depleting Trm by targeting the IL-15 axis may prove to be a highly effective and durable treatment for vitiligo and other autoimmune diseases.