Suppression of allogeneic response by viral IL-10 gene transfer.
Th1 cell activation and cytokine production shift the balance between Th1 and Th2, favoring the upregulation of proinflammatory activity that leads to destruction of allogeneic hepatocytes following transplantation. Th2-type cytokines. such as IL-10, have immune regulatory function. The aim of this study was to determine the antirejection efficacy of allogeneic hepatocytes with spheroidal shape (spheroids) genetically modified with viral IL-10 (vIL-10). Allogeneic hepatocyte spheroids, transferred vIL-10 gene by using adenovirus as the vector, were transplanted into the spleen of Nagase's analbuminemic rats (NAR). NAR transplanted with vIL-10-transfected hepatocytes showed an abrupt rise in serum albumin levels that peaked on day 7 and remained at high levels up to day 21 after transplantation. The peak level of albumin on day 7 in vIL-10-transfected NAR was eminently higher than that in nontransfected NAR. Histopathological analysis revealed that in nontransfected NAR hepatocyte spheroids were more or less rejected on day 4, and, in contrast, vIL-10-transfected spheroids were still not rejected on day 14. This protective effect correlated with sustained high vIL-10 level in the splenic vein in NAR transplanted with vIL-10-transfected hepatocyte spheroids, suggesting that vIL-10 secreted from the transplanted hepatocytes induced an active suppression of allogeneic response. This study provides evidence to support the possibility of using vIL-10 gene therapy to prevent allogeneic response in hepatocyte transplantation.
Fujisawa
Kenji
K
Department of Gastroenterological Surgery and Transplant, Okayama University Graduate School of Medicine and Dentistry, Okayama city, 700-8558 Japan.
Saito
Shinya
S
Okada
Yutaka
Y
Fujiwara
Toshiyosi
T
Yagi
Takahito
T
Iwagaki
Hiromi
H
Tanaka
Noriaki
N
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005697:Galactosides / Q000235:genetics; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006084:Graft Rejection / Q000517:prevention & control*; D022781:Hepatocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D007165:Immunosuppression Therapy / Q000379:methods*; D007211:Indoles; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000096:biosynthesis / Q000378:metabolism; D018874:Spheroids, Cellular / Q000276:immunology / Q000637:transplantation; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology / Q000379:methods
D005697:Galactosides; D007211:Indoles; D012709:Serum Albumin; D016753:Interleukin-10; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside