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


CONCLUSIONS
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.
Mulley
William R
WR
Molecular Immunogenetics Laboratory, The Austin Research Institute, Austin Health, Heidelberg, Vic., Australia.
Wee
Janet L
JL
Christiansen
Dale
D
Milland
Julie
J
Ierino
Francesco L
FL
Sandrin
Mauro S
MS
D000069594:Abatacept; D000818:Animals; D030801:Animals, Genetically Modified; D002460:Cell Line; D016207:Cytokines / Q000032:analysis*; D004730:Endothelium, Vascular; D005822:Genetic Vectors; D018796:Immunoconjugates / Q000235:genetics*; D016086:Lentivirus / Q000235:genetics*; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology*
D016207:Cytokines; D018796:Immunoconjugates; D000069594:Abatacept