Type 1 regulatory T cells(Tr1) are active in transplantation tolerance. The Tr1 cells are inducible in our lab from human CD4 T cells (hCD4 T) by hPDL1-overexpressed accessory A431 cells(human epidermoid cell line) in a way that at least one DR-DQ haplotype is shared between the hCD4 T and the PDL1+ A431. When A431 were substituted with PDL1-transfected porcine iliac artery endothelial cells(PIECs), hCD4 Tcould still be primed to differentiate into human Tr1 cells if the expression of swine SLA-DR, instead of SLA-DQ, on the PIECs was blocked with mAb. The activated Tr1 were potent for inducing suppression of xenogeneic mixed lymphocyte-endothelial cell response (xeno-MLER) by secreting IL-10 and TGF-beta. The PIECs were thus further cotransfected with mutated class II transactivator (mCIITA) and PDL1 genes to guarantee the cells with capabilities of stopping SLA-DR expression and inducing Tr1. Again,the resultant PDL1⁺SLA-DR^–PIECs functioned well for human Tr1 generation. Repeat stimulating hCD4 T cells with the mCIITA/PDL1-cotransfected PIECs left a CD4⁺CD25^–Foxp3^–IFN-γR⁺IL-10R⁺CD45RB^low Tr1 population at purity of 93.6% (3.8% in control), which down-regulated the xeno-MLER in a dose-dependent manner. It implicates that the hPDL1⁺SLA-DR^–PIECs are hopeful to be utilized as a cellular reagent for actively inducing regulatory Tr1 cells even in histoincompatible conditions.

CITATION INFORMATION: Shao Q, Diag Q. Human PDL1⁺ SLA-DR^– Swine Vascular Endothelial Cells Suppress Pig-Human PBMC Xeno-MLR(Mixed Lymphocyte Reaction) by Inducing Human Regulatory IL-10⁺Tr1(Type 1 Regulatory T Cells) Subset for Suppression of Xenogeneic Reactions. Am J Transplant. 2016;16 (suppl 3).

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