Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Bone Marrow Transplantation / adverse effects*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Flow Cytometry
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Graft vs Host Disease / etiology
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Graft vs Host Disease / immunology*
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Graft vs Host Disease / metabolism
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Humans
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Interleukin-18 / physiology*
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Interleukin-18 Receptor alpha Subunit
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Leukemia / blood
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Leukemia / therapy
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RNA, Messenger / biosynthesis
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Receptors, Interleukin / biosynthesis*
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Receptors, Interleukin / genetics
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Receptors, Interleukin / physiology
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Receptors, Interleukin-18
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Reverse Transcriptase Polymerase Chain Reaction
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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Transplantation, Homologous / adverse effects*
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Up-Regulation
Substances
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IL18R1 protein, human
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Interleukin-18
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Interleukin-18 Receptor alpha Subunit
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RNA, Messenger
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Receptors, Interleukin
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Receptors, Interleukin-18