Suppression of allogeneic response by viral IL-10 gene transfer

Kenji Fujisawa, Shinya Saito, Yutaka Okada, Toshiyoshi Fujiwara, Takahito Yagi, Hiromi Iwagaki, Noriaki Tanaka

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)379-387
Number of pages9
JournalCell Transplantation
Volume12
Issue number4
Publication statusPublished - 2003

Fingerprint

Gene transfer
Interleukin-10
Acetylglucosaminidase
Hepatocytes
Rats
Genes
Transplantation
Gene therapy
Th1-Th2 Balance
Splenic Vein
Cytokines
Th1 Cells
Adenoviridae
Serum Albumin
Genetic Therapy
Chemical activation
Albumins
Up-Regulation
Spleen

Keywords

  • Allogeneic response
  • Gene transfer
  • Hepatocyte transplantation
  • Viral IL-10

ASJC Scopus subject areas

  • Cell Biology
  • Transplantation

Cite this

Fujisawa, K., Saito, S., Okada, Y., Fujiwara, T., Yagi, T., Iwagaki, H., & Tanaka, N. (2003). Suppression of allogeneic response by viral IL-10 gene transfer. Cell Transplantation, 12(4), 379-387.

Suppression of allogeneic response by viral IL-10 gene transfer. / Fujisawa, Kenji; Saito, Shinya; Okada, Yutaka; Fujiwara, Toshiyoshi; Yagi, Takahito; Iwagaki, Hiromi; Tanaka, Noriaki.

In: Cell Transplantation, Vol. 12, No. 4, 2003, p. 379-387.

Research output: Contribution to journalArticle

Fujisawa, K, Saito, S, Okada, Y, Fujiwara, T, Yagi, T, Iwagaki, H & Tanaka, N 2003, 'Suppression of allogeneic response by viral IL-10 gene transfer', Cell Transplantation, vol. 12, no. 4, pp. 379-387.
Fujisawa, Kenji ; Saito, Shinya ; Okada, Yutaka ; Fujiwara, Toshiyoshi ; Yagi, Takahito ; Iwagaki, Hiromi ; Tanaka, Noriaki. / Suppression of allogeneic response by viral IL-10 gene transfer. In: Cell Transplantation. 2003 ; Vol. 12, No. 4. pp. 379-387.
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