Adoptive transfer of allogeneic T cells can lead to elimination of leukemic cells via graft-versus-leukemia reactivity, however, these cells may also cause potentially deadly graft-versus-host disease (GVHD). Ramadan et al. found that human or murine T9 cells (CD4+ and CD8+ cells differentiated under IL-4 and TGFβ) activated with IL-33 upregulate mST2, IL-9, PU.1, and amphiregulin expression, significantly reducing the severity of GVHD in mice. At the same time, T9IL-33 cells show enhanced CD8α expression for better killing of leukemia.
Allogeneic immune cells, particularly T cells in donor grafts, recognize and eliminate leukemic cells via graft-versus-leukemia (GVL) reactivity, and transfer of these cells is often used for high-risk hematological malignancies, including acute myeloid leukemia. Unfortunately, these cells also attack host normal tissues through the often fatal graft-versus-host disease (GVHD). Full separation of GVL activity from GVHD has yet to be achieved. Here, we show that, in mice and humans, a population of interleukin-9 (IL-9)-producing T cells activated via the ST2-IL-33 pathway (T9IL-33 cells) increases GVL while decreasing GVHD through two opposing mechanisms: protection from fatal immunity by amphiregulin expression and augmentation of antileukemic activity compared with T9, T1, and unmanipulated T cells through CD8alpha expression. Thus, adoptive transfer of allogeneic T9IL-33 cells offers an attractive approach for separating GVL activity from GVHD.
Author Info: (1) Indiana University School of Medicine, Indianapolis, IN. (2) Indiana University School of Medicine, Indianapolis, IN. (3) Indiana University School of Medicine, Indianapolis, I
Author Info: (1) Indiana University School of Medicine, Indianapolis, IN. (2) Indiana University School of Medicine, Indianapolis, IN. (3) Indiana University School of Medicine, Indianapolis, IN. (4) Indiana University School of Medicine, Indianapolis, IN. (5) Indiana University School of Medicine, Indianapolis, IN. (6) Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ. (7) Indiana University School of Medicine, Indianapolis, IN. (8) Indiana University School of Medicine, Indianapolis, IN sophpacz@iu.edu.
