Difference in the expression of Fas/Fas-ligand and the lymphocyte subset reconstitution according to the occurrence of acute GVHD.
Acute graft-versus-host disease (aGVHD) remains a major barrier to a wider application of allogeneic bone marrow transplantation (BMT). Although this complication is mainly dependent on donor-derived T lymphocytes, very little information is available concerning the mechanism of lethality. In this study, we investigated both the expression of Fas/Fas-ligand (FasL) and lymphocyte subset reconstitution in patients who underwent HLA-matched related allogeneic BMT (n = 16) and normal donors (n = 10), and several distinct features were observed. First, the reconstitutions of CD3+ and CD56+ cells were different between the aGVHD+ and aGVHD- group. In particular, the percentage of CD3-CD56+ cells was significantly decreased in patients with aGVHD (P < 0.01). Second, the expansion of CD8+ (P = 0.01) and CD8+ CD28- T cells (P = 0.03) was a characteristic finding in patients with aGVHD. Finally, we found that the percentages of Fas+CD8+, Fas+HLA-DR+ and FasL+ CD8+ cells were significantly increased. Fas antigen was highly coexpressed on most of the lymphocyte subsets, especially on CD8+ cells (P < 0.01), and also, significantly higher coexpression of FasL on CD8+ cells was found in patients with aGVHD (P < 0.01). In summary, an increase in the percentage of CD8+ cells which express Fas and its ligand in patients with aGVHD after BMT points to a possible role for the Fas/FasL pathway in the effector phase of aGVHD.
Lee
S
S
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
Chong
S Y
SY
Lee
J W
JW
Kim
S C
SC
Min
Y H
YH
Hahn
J S
JS
Ko
Y W
YW
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D053222:Fas Ligand Protein; D005260:Female; D005786:Gene Expression Regulation; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000628:therapy; D007958:Leukocyte Count; D018655:Lymphocyte Count; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014184:Transplantation, Homologous / Q000009:adverse effects; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor