Deregulation of endogenous IL-15 increases cholangiohepatitis and enteritis in recipients of allogeneic bone marrow transplants. (A) Upper panel: Cholangiohepatitis in animals with acute GVHD. Mononuclear inflammatory cells surround bile ducts (asterisks). Lesions shown in a liver harvested from a recipient of IL-15 tg B6 allogeneic BM cells (IL-15 tg allo) are more severe than those shown in a liver from a recipient of wt B6 allogeneic BM cells (wt allo) and include areas of hepatocyte necrosis (arrows). Bar = 50 μm. Lower panel: enteritis in animals with acute GVHD. There is a mononuclear inflammatory cell infiltrate in the lamina propria; crypts are hyperplastic and contain numerous mitotic figures. The intestine harvested from a recipient of IL-15 tg B6 allogeneic BM cells has more severe lesions than that harvested from a recipient of wt B6 allogeneic BM cells, including an area of crypt necrosis (arrow). Bar = 100 μm. Images were visualized using an Olympus BX41 microscope equipped with an Olympus 3040 camera and a Plan 20 × objective with an aperture of 0.40 (Olympus America, Melville, NY). The image medium was air, and the acquisition software was Adobe Photoshop (Adobe Systems, San Jose, CA). (B) Coded slides were scored by a veterinary pathologist in a blinded fashion as described in “Materials and methods.” Mice receiving IL-15 tg B6 allogeneic BM cells (solid bars) had significantly worse GVHD histopathology in the gut (P = .049) and liver (P = .004) compared with recipients of wt B6 allogeneic BM cells. Results are representative of 2 independent experiments involving a total of 12 mice.