Analysis of INF-gamma, TNF-alpha and dendritic cells to predict hepatitis C virus recurrence in liver transplant patients.
BACKGROUND
Hepatitis C virus (HCV) infection is one of the leading causes of chronic liver disease and the reason for more than 50% of liver transplantations (OLT). Recurrent HCV infection occurs in almost all transplant recipients and has an unfavorable course. Although immunosuppressive agents are necessary to avoid allograft rejection, these drugs may favor viral replication facilitating viral-mediated graft injury.


METHODS
To predict the evolution of two HCV(+) patients who underwent OLT, we studied INF-gamma and TNF-alpha production and the maturation capacity of dendritic cells (DCs) at three time points: before transplantation (Pre-Tx) and at 2 (2M) and 6 (6M) months after transplantation. Cytometric bead assays were used to quantify INF-gamma and TNF-alpha production in the supernates of mixed leukocyte reactions (MLR) between spleen cells from the liver donor and CD4(+) cells from the recipients. Immature and mature DCs were generated in vitro from patient monocytes.


RESULTS
The one patient who experienced recurrent HCV showed loss of CD4(+) responses to donor antigens and INF-gamma and TNF-alpha production after OLT. In contrast, the other patient maintained detectable levels of these cytokines after OLT. It was possible to generate mature DCs from monocytes with the aid of CD40L in both cases, but decreased expression of HLA-DR, CD80, and CD86 markers was observed upon posttransplantation analyses in the patient with recurrent HCV.


CONCLUSIONS
Loss of the proliferative response as well as INF-gamma and TNF-alpha production, together with a decreased HLA-DR, CD80, and CD86 (markers of mature DCs), indicated an inadequate immune response to viral progression in the liver transplant recipient with relapsing HCV infection.
Ocaña
L
L
Banc de Sang i Texits (BST), Barcelona, Spain. locana@vhebron.net
Cos
J
J
Quer
J
J
Bilbao
I
I
Palou
E
E
Parra
R
R
Sauleda
S
S
Esteban
J I
JI
Guàrdia
J
J
Massuet
L I
LI
Margarit
C
C
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D018122:B7-1 Antigen / Q000097:blood; D051940:B7-2 Antigen / Q000097:blood; D018791:CD4 Lymphocyte Count; D003713:Dendritic Cells / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000601:surgery*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood*; D016031:Liver Transplantation / Q000502:physiology*; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D011237:Predictive Value of Tests; D012008:Recurrence; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma