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

William Mulley, Janet Wee, Dale Christiansen, Julie Milland, F Lerino, Mauro Sandrin

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7 Citations (Scopus)

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-I?, 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. A? Blackwell Munksgaard, 2006.
Original languageEnglish
Pages (from-to)248 - 252
Number of pages5
JournalXenotransplantation
Volume13
Issue number3
DOIs
Publication statusPublished - 2006
Externally publishedYes

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