Lentiviral expression of CTLA4Ig inhibits primed xenogeneic lymphocyte proliferation and cytokine responses

Xenotransplantation. 2006 May;13(3):248-52. doi: 10.1111/j.1399-3089.2006.00297.x.

Abstract

Background: Co-stimulatory blockade is known to inhibit lymphocyte responses and to prolong allograft and xenograft survival. The present study examines the effect of transgenic expression of cytotoxic T lymphocyte-associated molecule-4 immunoglobulin (CTLA4Ig) by a porcine endothelial cell line (PIEC) transduced by a lentiviral vector, on primed xenogeneic T-cell proliferative and cytokine responses.

Methods: Splenocytes from mice primed with PIEC were used as responder cells in a secondary proliferative assay. CTLA4Ig transduced and wild-type PIEC were used as stimulator cells. Responder cells were assayed for proliferation and cytokine production.

Results: Proliferation was profoundly inhibited by CTLA4Ig transduced cells compared with control cells. Cytokine analysis by enzyme linked immunospot demonstrated that production of interferon-gamma, IL4 (interleukin 4) and IL10 was inhibited by CTLA4Ig transduced cells compared with control cells.

Conclusion: CTLA4Ig inhibited primed indirect xenogeneic T-cell proliferative and cytokine responses in vitro. Expression of immunomodulatory molecules by xenogeneic tissues has potential therapeutic applications for future xenotransplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abatacept
  • Animals
  • Animals, Genetically Modified
  • Cell Line
  • Cytokines / analysis*
  • Endothelium, Vascular
  • Genetic Vectors
  • Immunoconjugates / genetics*
  • Lentivirus / genetics*
  • Lymphocyte Activation
  • Lymphocyte Transfusion*
  • Mice
  • Mice, Inbred BALB C
  • Spleen / immunology
  • Swine
  • T-Lymphocytes / immunology*
  • Transplantation, Heterologous / immunology*

Substances

  • Cytokines
  • Immunoconjugates
  • Abatacept