Difference in the expression of Fas/Fas-ligand and the lymphocyte subset reconstitution according to the occurrence of acute GVHD

Abstract

Summary:mechanisms mediated by cytokines released from donorderived T cells. 1,2 Therefore, more detailed identification of T cell subsets can be an exceptionally good way to eluciAcute graft-versus-host disease (aGVHD) remains a major barrier to a wider application of allogeneic bone date the immune mechanism responsible for aGVHD. Recently accumulating evidence indicates that the Fas marrow transplantation (BMT). Although this complication is mainly dependent on donor-derived T lympho-(APO-1; CD95)/Fas-ligand (FasL) system represents an important cellular pathway responsible for T cell-mediated cytes, very little information is available concerning the mechanism of lethality. In this study, we investigated cytotoxicity and the induction of apoptosis in various tissues. [3][4][5] Fas antigen, which is a 45-kDa cell-surface type both the expression of Fas/Fas-ligand (FasL) and lymphocyte subset reconstitution in patients who underwent I membrane protein member of the tumor necrosis factor (TNF)/nerve growth factor receptor family, is expressed not HLA-matched related allogeneic BMT (n ‫؍‬ 16) and normal donors (n ‫؍‬ 10), and several distinct features only on activated T cells, but also on other tissues such as liver, heart, lung, skin and gastrointestinal tract. ؉ cells (P Ͻ 0.01), and also, significantly higher coexpression of FasL on However, Fas and FasL expression in aGVHD has not been further evaluated, and its clinical significance remains to be CD8 ؉ cells was found in patients with aGVHD (P Ͻ 0.01). In summary, an increase in the percentage elucidated in humans. Therefore, we evaluated both the lymphocyte subset of CD8 ؉ cells which express Fas and its ligand in patients with aGVHD after BMT points to a possible reconstitution and the expression of Fas and FasL on each lymphocyte subset in order to explore the pathogenesis of role for the Fas/FasL pathway in the effector phase of aGVHD.aGVHD based on Fas/FasL pathway.

Increased levels of immune transcript in patients with acute GVHD after allogeneic stem cell transplantation

“…Presently, only a few groups have analyzed immune transcript levels in humans after SCT. 15,16 In agreement with our hypothesis that acute GVHD is associated with the expression of a specific subset of immune activation genes, we determined that acute GVHD might be associated with an upregulation of the gene expressions of granzyme B, perforin and FasL. In the study, increased levels of these genes were detected in five out of five patients diagnosed with acute GVHD.…”

“…10 Several studies have also demonstrated the importance of the FasL and perforin pathways, as well as the TNF-a expression (or secretion) for the development of acute GVHD. [11][12][13][14][15][16] However, FasL, granzyme B, perforin and TNF-a gene expression in acute GVHD has not been further evaluated in stem cell transplanted patients, and its clinical significance remains to be elucidated in humans.…”

Increased soluble Fas-ligand in sera of bone marrow transplant recipients with acute graft-versus-host disease

“…14 In addition, an increase in the percentage of CD8 + cells which express FasL in patients with aGVHD has been demonstrated. 15 The relationship between the Fas/FasL system and the development of aGVHD is complex. Activated Fas/FasL system may be responsible for the tissue damage associated with aGVHD.…”

IFN-γ and Fas Ligand Are Required for Graft-versus-Tumor Activity against Renal Cell Carcinoma in the Absence of Lethal Graft-versus-Host Disease

“…The effector mechanisms that have been studied include the Fas/Fas ligand (FasL), perforin/granzyme, and TRAIL/DR5 pathways and several cytokines, including TNF-␣ and IFN-␥ (2). Aside from differences in the results of several experimental models, most studies indicate an important role for Fas/FasL in systemic and liver GVHD (3)(4)(5), while TNF-␣ seems to be involved in intestinal GVHD (6 -8). Conversely, different pathways have been described in GVL activity.…”

“…A llogeneic bone marrow transplantation (allo-BMT) 3 is an effective therapeutic strategy for hematological malignancies. Its therapeutic efficacy could be enhanced by facilitating the capacity of donor T cells to react against tumor cells, i.e., graft-versus-leukemia (GVL) effect, while avoiding graft-versus-host disease (GVHD), the primary complication of this therapy (1).…”