The role of donor T cells for target organ injuries in acute and chronic graft-versus-host disease

Donor T cells are crucial for target organ injury in graft-versus-host dise ase (GVHD). We examined the effects of donor T cells on the target organs u sing a parent-into-FI model of acute and chronic GVHD. Donor T cells showed engraftment in the spleen, small intestine and liver of mice with acute GV HD, causing typical GVHD pathology in these organs. Interferon-gamma and Fa s ligand expression were up-regulated, and host lymphocytes were depleted i n the target organs of these mice. In contrast, donor T cells did not show engraftment in the small intestine of mice with chronic GVHD, and no GVHD p athology was observed in this organ. However, both donor T-cell engraftment and GVHD pathology were observed in the spleen and liver of chronic GVHD m ice, along with the up-regulation of interleukin-4 (IL-4) and IL-10 express ion plus the expansion of host lymphocytes such as splenic B cells and hepa tic natural killer (NK) 1.1(+) T cells. Donor anti-host cytotoxic T-lymphoc yte activity was observed in spleen cells from mice with acute GVHD, but no t in spleen cells from mice with chronic GVHD. Transplantation of Fas ligan d-deficient (gld) spleen cells did not induce host lymphocyte depletion in target organs. These results indicate that donor T cells augment type 1 T h elper immune responses and deplete the host lymphocytes from target organs mainly by Fas-mediated pathways in acute GVHD, while donor T cells augment type 2 T helper immune responses and expand host splenic B cells and hepati c NK1.1(+) T cells in chronic GVHD.