title: Enrichment of regulatory T cells in acutely rejected human liver allografts.
abstract: Acute cellular rejection (ACR) occurs frequently after liver transplantation and can usually be controlled. Triggering of allospecific immune responses and lack of immunoregulation are currently suggested as a cause of ACR, but there are no investigations of intrahepatic immune responses during ACR. Therefore we prospectively analyzed the intrahepatic T cell infiltration pattern in correlation to the severity of ACR in a cohort of patients with graft hepatitis (n = 151). While CD4(+)  cells dominated the portal infiltrates in mild-moderate ACR, CD8(+)  cells prevailed in severe ACR. Furthermore portal CD8(+)  and not CD4(+)  infiltration correlated with serum transaminases and with the likelihood of subsequent ACRs. Surprisingly, the rise of portal effector T cells density during ACR was surpassed by the increase in portal infiltration of regulatory T cells by a factor of two. Thus ACRs rather showed an increase and not a lack of regulation, as was suggested by analysis of peripheral blood mononuclear cells. Despite the pattern of enhanced immunoregulation, patients with severe ACR had a higher risk for subsequent rejections and showed a trend to a reduced survival. Thus, patients with severe rejections might need a modification of their immunosuppression to improve prognosis.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Taubert
authors.forename: S
authors.initials: S
authors.lastname: Pischke
authors.forename: J
authors.initials: J
authors.lastname: Schlue
authors.forename: H
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: F
authors.initials: F
authors.lastname: Noyan
authors.forename: A
authors.initials: A
authors.lastname: Heim
authors.forename: F
authors.initials: F
authors.lastname: Lehner
authors.forename: H
authors.initials: H
authors.lastname: Barg-Hock
authors.forename: J
authors.initials: J
authors.lastname: Klempnauer
authors.forename: S
authors.initials: S
authors.lastname: Olek
authors.forename: M P
authors.initials: MP
authors.lastname: Manns
authors.forename: M
authors.initials: M
authors.lastname: Hardtke-Wolenski
authors.forename: E
authors.initials: E
authors.lastname: Jaeckel
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008111:Liver Function Tests; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014184:Transplantation, Homologous