PB2384 EFFECTS OF IMMUNOSUPPRESSIVE DRUGS FREQUENTLY USED IN THE PREVENTION AND TREATMENT OF GRAFT‐VERSUS‐HOST DISEASE ON INNATE LYMPHOID CELL FUNCTION AND SURVIVAL

Background: Graft‐versus‐host disease (GvHD) is an inflammatory disease that frequently occurs after allogeneic hematopoietic stem cell transplantation (allo‐HSCT). In GvHD, donor T cells are harmful and cause damage to recipients’ healthy tissue. Other immune cells such as innate lymphoid cells (ILCs) are beneficial, as they are important for the maintenance and repair of epithelial barriers. ILC3s for example, produce interleukin (IL)‐22, a cytokine important for intestinal epithelial cell homeostasis, and regulatory ILCs can suppress T‐cell activation. We have previously shown that higher ILC counts before and after allo‐HSCT were associated with a reduced risk to develop GvHD. Following allogeneic HSCT, immunosuppressive drugs are used to prevent and treat GvHD. However, such immunosuppressive medications could potentially suppress the beneficial effects of ILCs. Aims: We investigate the effect of immunosuppressive drugs frequently used in the prevention and treatment of GvHD on the survival, proliferation, activation and function of ILCs in vitro . Methods: Tonsil‐derived T cells and ILC3s were FACS sorted and labeled with the CellTrace TM Violet dye. After 24‐h rest, T cells were stimulated with anti‐CD3/CD28 beads and ILC3s were stimulated with IL‐2, IL‐1β and IL‐23. After stimulation (1 hour), immune suppressants or vehicle control were added to both cell types. After 4 days of incubation, cytokine production was analyzed by ELISA and cell survival, proliferation and activation was analyzed by flow cytometry. Results: Prednisolone had similar effects on T cells and ILC3s. It inhibited cytokine production by both cell types, but did not affect T cell and ILC3 proliferation or activation. However, non‐cytotoxic concentrations of methotrexate (MTX), mycophenolic acid (MMF) and imatinib (Gleevec) differentially affected T cells and ILCs. MTX suppressed T cell proliferation and activation but had no effect on ILC3s. MMF inhibited T cell proliferation, but did not affect activation or cytokine production of either cell type. Finally, imatinib suppressed T cell proliferation, activation and function, but had no effect on ILC3 proliferation and function. Other immunosuppressive compounds are currently under investigation. Summary/Conclusion: Our data demonstrate that commonly used immunosuppressive drugs directed at suppressing T‐cell function and applied to prevent and treat GvHD can have different effects on ILC activation, proliferation and function. These findings will help to develop strategies to maximize the use of the protective function of ILCs in addition to suppressing T cell alloreactivity, in the prevention and treatment of GvHD.