Third Party Type 2 Innate Lymphoid Cells Prevent and Treat GI Tract GvHD.

Acute GvHD, mediated by the recognition of host MHC/peptide polymorphisms by donor T cells, remains a significant complication of allogeneic hematopoietic stem cell transplantation (A-HSCT). Acute GvHD most commonly involves the gastrointestinal tract, liver and skin; symptomatic acute GvHD is treated with corticosteroids. Steroid non-responsive acute GvHD is a significant problem for patients undergoing A-HSCT with less than 15% of these patients alive one year after diagnosis. Previously, we demonstrated that the infusion of donor innate lymphoid type II (ILC2) cells could prevent and treat acute GvHD of the lower GI tract with no effect on the GvL response. This approach for clinical translation is cumbersome as it would require the generation of donor-derived ILC2 cells for each recipient. Thus, the ability to use third party ILC2 cells would provide an "off the shelf" reagent that could be used to treat and/or prevent acute GvHD. Here, we show that third party ILC2 cells enhance the survival of allogeneic A-HSCT recipients. Treatment required at least four weekly infusions of ILC2 cells. Mechanistically, we demonstrate that ILC2 cell function was completely lost if the cells could not express both IL-13 and amphiregulin. Finally, we show that the activity of IL-13 has a greater dependence on the expression of the IL-13R on host rather than donor BM cells. The ability to generate third party ILC2 cells offers a new avenue for the prevention of acute GvHD.