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

Abstract

Donor T cells are crucial for target organ injury in graft‐versus‐host disease (GVHD). We examined the effects of donor T cells on the target organs using a parent‐into‐F₁ model of acute and chronic GVHD. Donor T cells showed engraftment in the spleen, small intestine and liver of mice with acute GVHD, causing typical GVHD pathology in these organs. Interferon‐γ and Fas ligand expression were up‐regulated, and host lymphocytes were depleted in 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 pathology was observed in this organ. However, both donor T‐cell engraftment and GVHD pathology were observed in the spleen and liver of chronic GVHD mice, along with the up‐regulation of interleukin‐4 (IL‐4) and IL‐10 expression plus the expansion of host lymphocytes such as splenic B cells and hepatic natural killer (NK) 1.1⁺ T cells. Donor anti‐host cytotoxic T‐lymphocyte activity was observed in spleen cells from mice with acute GVHD, but not in spleen cells from mice with chronic GVHD. Transplantation of Fas ligand‐deficient (gld) spleen cells did not induce host lymphocyte depletion in target organs. These results indicate that donor T cells augment type 1 T helper 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 hepatic NK1.1⁺ T cells in chronic GVHD.