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

Abstract

SUMMARYDonor 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-F 1 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-c 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

Preferential Involvement of Tim-3 in the Regulation of Hepatic CD8+ T Cells in Murine Acute Graft-versus-Host Disease

“…In aGVHD, the activation of T cells and the ensuing production and release of inflammatory cytokine causes a systemic illness characterized by immunosuppression and tissue destruction of various organs, including liver, intestinal mucosa, and skin (15)(16)(17). Hepatic GVHD is characterized by donor T cell activation in the induction phase and by inflammatory reactions in the effector phase (18 -20).…”

Early-phase GVHD gene expression profile in target versus non-target tissues: kidney, a possible target?

“…Hypothetically all organs should be possible targets for donor T cells; nevertheless, the liver, gastrointestinal tract, skin and lungs 3,5,6 are the principal target organs. 7 Although damage to other organs (for example, kidney) has been described, 8,9 most clinicians do not consider the kidney a target organ for acute GVHD (aGVHD). Several hypotheses have been discussed, but clear alterations of target versus non-target tissues have not been explored yet.…”

Delayed or delayed sequential bone marrow transplantation: relevance for acute graft-versus-host disease prevention after major H2 incompatible transplantation

“…The conditioning regimen simultaneously damages and activates host tissues, amplifying antigen presentation to allogeneic donor T cells. [11][12][13][14][15] TBI and large doses of cyclophosphamide 3,4 have been shown to induce host inflammatory cytokine release. These cytokines cause or aggravate host tissue damage 16 and modulate MHC antigen expression.…”