NKp46⁺ innate lymphoid cells dampen vaginal CD8 T cell responses following local immunization with a cholera toxin-based vaccine

Innate and adaptive immune cells work in concert to generate efficient protection at mucosal surface. Vaginal mucosa is an epithelial tissue that contains innate and adaptive immune effector cells. Our previous studies demonstrated that vaginal administration of Cholera toxin -based vaccines generate antigen-specific CD8 T cells through the stimulation of local dendritic cells (DC). Innate lymphoid cells (ILC) are a group of lymphocytes localized in epithelial tissues that have important immune functions against pathogens and in tissue homeostasis. Their contribution to vaccine-induced mucosal T cell responses is an important issue for the design of protective vaccines. We report here that the vaginal mucosa contains a heterogeneous population of NKp46⁺ ILC that includes conventional NK cells and ILC1-like cells. We show that vaginal NKp46⁺ ILC dampen vaccine-induced CD8 T cell responses generated after local immunization. Indeed, in vivo depletion of NKp46⁺ ILC with anti-NK1.1 antibody or NKG2D blockade increases the magnitude of vaginal OVA-specific CD8 T cells. Furthermore, such treatments also increase the number of DC in the vagina. NKG2D ligands being expressed by vaginal DC but not by CD8 T cells, these results support that NKp46⁺ ILC limit mucosal CD8 T cell responses indirectly through the NKG2Ddependent elimination of vaginal DC. Our data reveal an unappreciated role of NKp46⁺ ILC in the regulation of mucosal CD8 T cell responses.