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Enrichment of Regulatory T Cells in Acutely Rejected Human Liver Allografts
Author(s) -
Taubert R.,
Pischke S.,
Schlue J.,
Wedemeyer H.,
Noyan F.,
Heim A.,
Lehner F.,
BargHock H.,
Klempnauer J.,
Olek S.,
Manns M. P.,
HardtkeWolenski M.,
Jaeckel E.
Publication year - 2012
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2012.04264.x
Subject(s) - medicine , immunosuppression , liver transplantation , infiltration (hvac) , cd8 , immune system , peripheral blood mononuclear cell , regulatory t cell , immunology , effector , gastroenterology , t cell , transplantation , pathology , il 2 receptor , biology , biochemistry , physics , in vitro , thermodynamics
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.