title: Differential upregulation of interleukin-18 receptor alpha chain between CD4+ and CD8+ T cells during acute graft-versus-host disease in mice.
abstract: Interleukin-18 (IL-18), a unique cytokine that stimulates both T helper 1 (Th1) and Th2 responses, is associated with acute graft-versus-host disease (aGVHD), the major limiting toxicity following allogeneic stem cell transplantation. Here, we investigated the mechanism underlying the upregulation of IL-18 receptor (IL-18R) expression on T cells in murine aGVHD models. The induction of aGVHD elevated host serum IL-12 levels and increased expression of IL-18Ralpha chain (IL-18Ralpha) on engrafted T cells, in particular on CD8+ T cells. However, IL-18Ralpha expression did not increase on the CD4+ T cells of an IL-12-deficient host, indicating the IL-12-dependent upregulation of IL-18Ralpha expression on CD4+ T cells during aGVHD. Purified donor CD8+ T cells transferred in the host increased IL-18Ralpha expression. In vitro experiments showed that IL-18Ralpha expression upregulated on CD8+ T cells but not on CD4+ T cells on stimulation through the T cell receptor (TCR). These results suggest that IL-18Ralpha expression is differentially upregulated between CD4+ and CD8+ T cells during aGVHD, depending on endogenous IL-12 and TCR engagement, respectively.
authors.affiliation: Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Hisayuki
authors.initials: H
authors.lastname: Itoi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimori
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Matsui
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Hada
authors.forename: Eizo
authors.initials: E
authors.lastname: Kakishita
authors.forename: Haruki
authors.initials: H
authors.lastname: Okamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hara
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakanishi
mesh_terms: D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D017690:Cell Transplantation; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology; D053727:Interleukin-18 Receptor alpha Subunit; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018123:Receptors, Interleukin / Q000096:biosynthesis / Q000276:immunology*; D053724:Receptors, Interleukin-18; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology; D015854:Up-Regulation
chemical_list: C508573:Il18r1 protein, mouse; D053727:Interleukin-18 Receptor alpha Subunit; D011948:Receptors, Antigen, T-Cell; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18; D018664:Interleukin-12