Volume 13, Issue 3 pp. 248-252

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

William R Mulley

William R Mulley

Molecular Immunogenetics Laboratory, The Austin Research Institute, Austin Health, Heidelberg, Vic., Australia

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Janet L Wee

Janet L Wee

Molecular Immunogenetics Laboratory, The Austin Research Institute, Austin Health, Heidelberg, Vic., Australia

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Dale Christiansen

Dale Christiansen

Molecular Immunogenetics Laboratory, The Austin Research Institute, Austin Health, Heidelberg, Vic., Australia

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Julie Milland

Julie Milland

Molecular Immunogenetics Laboratory, The Austin Research Institute, Austin Health, Heidelberg, Vic., Australia

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Francesco L. Ierino

Francesco L. Ierino

Molecular Immunogenetics Laboratory, The Austin Research Institute, Austin Health, Heidelberg, Vic., Australia

Department of Nephrology, Austin Health, Heidelberg, Vic., Australia

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Mauro S. Sandrin

Mauro S. Sandrin

Molecular Immunogenetics Laboratory, The Austin Research Institute, Austin Health, Heidelberg, Vic., Australia

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First published: 31 May 2006
Citations: 8
Address reprint requests to Professor Mauro Sandrin, Molecular Immunogenetics Laboratory, The Austin Research Institute, Austin Health, Studley Rd, Heidelberg, Vic. 3084, Australia
(E-mail: [email protected])

Abstract

Mulley WR, Wee JL, Christiansen D, Milland J, Ierino FL, Sandrin MS. Lentiviral expression of CTLA4Ig inhibits primed xenogeneic lymphocyte proliferation and cytokine responses.
Xenotransplantation 2006; 13: 248–252. © Blackwell Munksgaard, 2006

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-γ, 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.

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