title: Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humans.
abstract: We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8(+) alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8(+)CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27(-)CD28(-) subsets, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12Rbeta1(+) cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance.
authors.affiliation: Department of Surgery, Faculty of Medicine, Kyoto University, Kyoto, Japan. egawa@kuhp.kyoto-u.ac.jp
authors.forename: Hiroto
authors.initials: H
authors.lastname: Egawa
authors.forename: Shingi
authors.initials: S
authors.lastname: Uemoto
authors.forename: Yasutugu
authors.initials: Y
authors.lastname: Takada
authors.forename: Kazue
authors.initials: K
authors.lastname: Ozawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Teramukai
authors.forename: Hironori
authors.initials: H
authors.lastname: Haga
authors.forename: Mureo
authors.initials: M
authors.lastname: Kasahara
authors.forename: Kouhei
authors.initials: K
authors.lastname: Ogawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sato
authors.forename: Masako
authors.initials: M
authors.lastname: Ono
authors.forename: Kenji
authors.initials: K
authors.lastname: Takai
authors.forename: Masanori
authors.initials: M
authors.lastname: Fukushima
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D016063:Blood Loss, Surgical; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000601:surgery; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000601:surgery; D016031:Liver Transplantation / Q000276:immunology / Q000502:physiology*; D019520:Living Donors / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones