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Title: Lentiviral expression of CTLA4Ig inhibits primed xenogeneic lymphocyte proliferation and cytokine responses.
Austin Authors: Mulley, William R;Wee, Janet L;Christiansen, Dale;Milland, Julie;Ierino, Francesco L;Sandrin, Mauro S 
Affiliation: Molecular Immunogenetics Laboratory, The Austin Research Institute, Austin Health, Heidelberg, Victoria, Australia
Issue Date: 1-May-2006
Publication information: Xenotransplantation; 13(3): 248-52
Abstract: 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.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.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.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.
Gov't Doc #: 16756567
DOI: 10.1111/j.1399-3089.2006.00297.x
Journal: Xenotransplantation
Type: Journal Article
Subjects: Animals
Animals, Genetically Modified
Cell Line
Endothelium, Vascular
Genetic Vectors
Lymphocyte Activation
Lymphocyte Transfusion
Mice, Inbred BALB C
Transplantation, Heterologous.immunology
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