Increased expression of interleukin-18 receptor on T lymphocytes in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation.
Acute graft-versus-host disease (aGVHD), a potentially fatal side effect of allogeneic bone marrow transplantation (BMT), is initiated by the action of donor-derived T lymphocytes. We have shown previously that aGVHD is associated with elevated serum levels of interleukin-18 (IL-18). In this study, we analyzed the expression of the IL-18 receptor (IL-18R) on T lymphocytes of BMT patients with aGVHD. Flow cytometric analysis showed that in healthy subjects, a small population of CD4+ T cells expressed IL-18Ralpha, whereas a relatively large population of CD8+ T cells expressed IL-18Ralpha. In aGVHD patients, there were marked increases in the proportion of CD4+ or CD8+ T cells that express IL-18Ralpha. RT-PCR assays showed elevation of IL-18Ralpha and IL-18Rbeta mRNA levels in CD8+ T cells in aGVHD patients. These findings suggest that the expression of IL-18R is upregulated in T cells in patients with aGVHD and that the IL-18/IL-18R system is active during aGVHD.
Laboratory of Cell Transplantation, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Japan. fuji-y@hyo-med.ac.jp
Yoshihiro
Y
Fujimori
Tomohiro
T
Yoshimoto
Kiyoshi
K
Matsui
Hiroko
H
Tsutsui
Takahiro
T
Okamoto
Shin-Ichiro
S
Kashiwamura
Toshikazu
T
Hada
Haruki
H
Okamura
Eizo
E
Kakishita
Hiroshi
H
Hara
Kenji
K
Nakanishi
D000208:Acute Disease; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D020382:Interleukin-18 / Q000502:physiology*; D053727:Interleukin-18 Receptor alpha Subunit; D007938:Leukemia / Q000097:blood / Q000628:therapy; D012333:RNA, Messenger / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D053724:Receptors, Interleukin-18; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D014184:Transplantation, Homologous / Q000009:adverse effects*; D015854:Up-Regulation
C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18