Adoptive transfer of donor-derived immunity by liver transplantation

TY - JOUR

T1 - Adoptive transfer of donor-derived immunity by liver transplantation

T2 - a potential avenue to prevent hepatitis B virus reinfection

AU - Dahmen, U

AU - Dirsch, O

AU - Gu, Y L

AU - Polywka, S

AU - Doebel, L

AU - Shen, K

AU - Broelsch, C E

PY - 2003/1

Y1 - 2003/1

N2 - Immunity to hepatitis B has been successfully transferred by bone marrow transplantation, but has also occurred after liver transplantation (LTx). This study was designed to analyse the influence of alloreactivity and immunosuppression, on the efficacy of adoptive immune transfer to hepatitis B by liver transplantation. Orthotopic LTx (n = 34) were performed in three rat strain combinations representing different genetic constellations. Donors had been vaccinated twice with recombinant hepatitis B surface antigen while recipients were unimmunized. Half of the allogeneic recipients were immunosuppressed with cyclosporin A. All animals were monitored weekly for the presence of anti-hepatitis B surface antibodies (anti-HBs). Effective anti-HBs titres were detected in 85% (29/34) of liver recipients and lasted from 2 to 10 weeks. Donor titre above >15 000 mIU/mL ensured a 100% seroconversion rate in the recipients. The maximal anti-HBs titre in recipients represented 0.06% approximately 0.76% of the donor titre. Rejection reduced the adoptive immune transfer, which was protected by immunosuppression. These observations suggest that transfer of functionally active donor lymphocytes, deriving from the graft, contributed to the donor-derived immune response in the recipient. Further studies to augment the donor-derived immune response are warranted to ensure a therapeutic effect for the recipient at risk of reinfection.

AB - Immunity to hepatitis B has been successfully transferred by bone marrow transplantation, but has also occurred after liver transplantation (LTx). This study was designed to analyse the influence of alloreactivity and immunosuppression, on the efficacy of adoptive immune transfer to hepatitis B by liver transplantation. Orthotopic LTx (n = 34) were performed in three rat strain combinations representing different genetic constellations. Donors had been vaccinated twice with recombinant hepatitis B surface antigen while recipients were unimmunized. Half of the allogeneic recipients were immunosuppressed with cyclosporin A. All animals were monitored weekly for the presence of anti-hepatitis B surface antibodies (anti-HBs). Effective anti-HBs titres were detected in 85% (29/34) of liver recipients and lasted from 2 to 10 weeks. Donor titre above >15 000 mIU/mL ensured a 100% seroconversion rate in the recipients. The maximal anti-HBs titre in recipients represented 0.06% approximately 0.76% of the donor titre. Rejection reduced the adoptive immune transfer, which was protected by immunosuppression. These observations suggest that transfer of functionally active donor lymphocytes, deriving from the graft, contributed to the donor-derived immune response in the recipient. Further studies to augment the donor-derived immune response are warranted to ensure a therapeutic effect for the recipient at risk of reinfection.

KW - Animals

KW - Bone Marrow Transplantation

KW - Disease Models, Animal

KW - Graft Survival

KW - Hepatitis B

KW - Hepatitis B Antibodies

KW - Hepatitis B Surface Antigens

KW - Hepatitis B Vaccines

KW - Immunosuppression

KW - Immunotherapy, Adoptive

KW - Liver Transplantation

KW - Male

KW - Rats

KW - Rats, Inbred ACI

KW - Rats, Inbred BN

KW - Rats, Inbred Lew

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

M3 - SCORING: Journal article

C2 - 12558909

VL - 10

SP - 31

EP - 36

JO - J VIRAL HEPATITIS

JF - J VIRAL HEPATITIS

SN - 1352-0504

IS - 1

ER -