Regulating the expression of CD80/CD86 on dendritic cells to induce immune tolerance after xeno-islet transplantation

Immunobiology
Nengwen KeZhao-da Zhang

Abstract

Antigen present cells (APCs) have been demonstrated to play dual roles in immune tolerance. Recently, compelling evidence indicates that APCs that express CD80, but not CD86 can protect allograft. We investigated whether modulation of CD80 in dendritic cells (DCs) offer protection for xeno-islets. In vitro, isolated mature murine DCs received untransfection, transfection with CD86 siRNA or negative control siRNA. The DCs were used in mixed lymphocyte reaction in which rat islets and murine splenocytes were further added. On day 3 of co-culturing, the proliferation of lymphocytes was measured and interleukin (IL)-2, IL-4, IL-10, transforming growth factor β (TGF-β), interferon γ (INF-γ) and indoleamine 2,3-dioxygenase (IDO) from the supernatants were determined. Islets viability and function were also assessed. In vivo, streptozotocin-induced diabetic mice underwent rat islets transplantation were pre-treated with above DCs. At designated time, xeno-islets were subjected to histopathology, immunohistochemistry, survival time and functional tests. Peripheral blood T lymphocyte profiles were also examined. CD86-silenced-DCs had unchanged expression of CD80 and significantly suppressed the proliferation of lymphocytes. CD86-silence...Continue Reading

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Citations

Apr 24, 2016·Xenotransplantation·Christopher Burlak
Jun 13, 2018·Nucleic Acid Therapeutics·Francesco MaininiMichael R Eccles
Apr 9, 2020·Frontiers in Immunology·Yongbo ZhaoLiping Jin
Jun 7, 2019·Current Opinion in Organ Transplantation·Charles G Rickert, James F Markmann
Oct 12, 2021·Archivum Immunologiae Et Therapiae Experimentalis·Maja MachcińskaGrażyna Korczak-Kowalska
Aug 26, 2018·International Journal of Biological Macromolecules·Zhenguang LiuDeyun Wang

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