Porcine CTLA4-Ig prolong islet xenografts in rats by downregulating the direct pathway of T-cell activation

Xenotransplantation. Jan-Feb 2011;18(1):40-5. doi: 10.1111/j.1399-3089.2011.00627.x.

Abstract

Aim: Porcine pancreatic islets fused with pCTLA4-Ig were transplanted into diabetic rats. Xenografts survival was observed, and the underlying immunological rejection mechanisms were investigated.

Methods: Control porcine islets, empty vector (Adv-GFP)-transfected, and gene-modified porcine islets were transplanted into the renal capsule of diabetic rats. The survival rates of the xenografts were observed. Changes in serum levels of IL-4 and γ-IFN in the recipients were assessed.

Results: The survival time of xenografts in the gene-modified porcine islets group was 34.50 ± 4.14 days, which was longer than those in the control group (34.50 ± 4.14 days vs. 7.43 ± 1.72 days and 7.22 ± 1.72 days; P < 0.01). Changes in the serum levels of IL-4 and γ-IFN between the groups of rats post-transplantation indicated the differentiation bias of T helper cells.

Conclusions: The donor-originated pCTLA-IgG4 fusion protein inhibits the direct pathway of recipient T-cell priming, which might prolong xenograft survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Animals
  • Diabetes Mellitus / immunology
  • Diabetes Mellitus / therapy
  • Graft Survival
  • Humans
  • Immunoconjugates / genetics
  • Immunoconjugates / immunology*
  • Immunosuppressive Agents / immunology*
  • Islets of Langerhans Transplantation / immunology*
  • Lymphocyte Activation / immunology*
  • Rats
  • Rats, Sprague-Dawley
  • Sus scrofa
  • T-Lymphocytes / immunology*
  • Transplantation, Heterologous / immunology*

Substances

  • Immunoconjugates
  • Immunosuppressive Agents
  • Abatacept