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 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-gamma 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.
Kataoka
Y
Y
Second Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan.
Iwasaki
T
T
Kuroiwa
T
T
Seto
Y
Y
Iwata
N
N
Hashimoto
N
N
Ogata
A
A
Hamano
T
T
Kakishita
E
E
D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology; D008024:Ligands; D008099:Liver / Q000276:immunology; D017710:Lymphocyte Transfusion; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000276:immunology / Q000637:transplantation; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019014:fas Receptor / Q000378:metabolism
D016207:Cytokines; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor