Adoptive transfer of donor-derived immunity by liver transplantation: a potential avenue to prevent hepatitis B virus reinfection.
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.
Dahmen
U
U
Department of General and Transplantation Surgery, University Hospital Essen, Essen, Germany. uta.dahmen@uni-essen.de
Li
J
J
Dirsch
O
O
Gu
Y L
YL
Polywka
S
S
Doebel
L
L
Shen
K
K
Broelsch
C E
CE
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004195:Disease Models, Animal; D006085:Graft Survival; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control; D006510:Hepatitis B Antibodies / Q000097:blood* / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000097:blood; D017325:Hepatitis B Vaccines / Q000627:therapeutic use; D007165:Immunosuppression Therapy / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew
D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines