title: Increased intragraft IL-15 mRNA expression after liver transplantation.
abstract: To study T-cell/macrophage interactions at the molecular level in clinical allograft rejection, we measured intragraft mRNA expression of the T-cell derived cytokine IL-2 and the macrophage derived chemokine IL-15, a novel cytokine associated with T-cell activation, in post-transplant liver biopsies (n = 33) and in non-transplanted control liver tissue by reverse transcriptase-polymerase chain reaction (RT-PCR). We analyzed biopsies without evidence of rejection (n = 12), with spontaneously resolving histological rejection (n = 10), or with histological rejection accompanied with clinical rejection (n = 11) defined by rising serum bilirubin and aspartate amino transaminase levels. IL-15 mRNA expression was present in the majority of post-transplant liver biopsies (91%, 30/33) and was significantly upregulated as compared with non-transplanted liver tissue (p = 0.005). However, the increased intragraft IL-15 mRNA level was not indicative for rejection. In contrast to intragraft IL-15 mRNA expression, IL-2 mRNA transcription was measured in the minority of the post-transplant liver biopsies (15%, 5/33) and not detectable in control specimens. In addition, IL-2 mRNA was almost specifically measured in rejection biopsies concurrent with graft dysfunction (36%, 4/11 versus 1/22 without clinical rejection; p = 0.03). No relation between intragraft IL-2 and IL-15 mRNA expression was found. The IL-15 mRNA expression levels were not higher in the IL-2 negative rejections compared with those in IL-2 positive rejections. To conclude, in contrast to IL-2, the function of IL-15 in T-cell mediated rejection remains unclear. The overall high IL-15 mRNA levels in sites of immune responses suggests that the macrophage-derived mediator IL-15 is involved in a constant flow of T-cells from the circulation into the graft.
authors.affiliation: Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands. baan@inw1.azr.nl
authors.forename: C C
authors.initials: CC
authors.lastname: Baan
authors.forename: H G
authors.initials: HG
authors.lastname: Niesters
authors.forename: H J
authors.initials: HJ
authors.lastname: Metselaar
authors.forename: W M
authors.initials: WM
authors.lastname: Mol
authors.forename: E H
authors.initials: EH
authors.lastname: Loonen
authors.forename: P E
authors.initials: PE
authors.lastname: Zondervan
authors.forename: H W
authors.initials: HW
authors.lastname: Tilanus
authors.forename: J M
authors.initials: JM
authors.lastname: IJzermans
authors.forename: S W
authors.initials: SW
authors.lastname: Schalm
authors.forename: W
authors.initials: W
authors.lastname: Weimar
mesh_terms: D001706:Biopsy; D004587:Electrophoresis, Agar Gel; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019409:Interleukin-15; D007376:Interleukin-2; D012333:RNA, Messenger