Organ supply remains the primary barrier to liver transplantation. Xenotransplantation provides a potential source to meet this shortage. HD antigen is a known xenoantigen to which humans have antibodies. We examined the human xenogeneic cellular response to GalT-KO/CMAH-KO.
Mixed lymphocyte reactions were performed utilizing human PBMCs against GalT-KO/CMAH-KO and GalTKO swine PBMCs in triplicate. Stimulation index was similar against GalT-KO/CMAH-KO as compared to GalTKO PBMCs as shown in two representative samples.
Inhibition of direct activation by anti-SLA class II antibody resulted in a more significant decrease in stimulation index against GalT-KO/CMAH-KO as compared to GalTKO PBMCs.
The stimulation of human PBMCs by GalT-KO/CMAH-KO PBMCs was suppressed by tacrolimus co-incubation at 0.1, 1 and 5 ng/mL. Stimulation index was decreased by 55%, 60% and 67%, respectively.
Progressive elimination of the humoral xenogeneic barrier does not remove the cellular xenogeneic response. This study demonstrates an increased cellular response relative to previous potential genetically engineered swine donors, but this response seems to be mitigated with clinically relevant immunosuppression. In addition, there appears to be an increased direct xenogeneic response to GalT-KO/CMAH-KO PBMCs, indicating possible greater compatibility of the GalT-KO/CMAH-KO SLA Class II and human T-cell receptor.
To cite this abstract in AMA style:Shah A, Sidner R, Paris L, Estrada J, Tector A. Human Anti-Pig Xenogeneic T-Cell Response in the Absence of HD Antigen [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/human-anti-pig-xenogeneic-t-cell-response-in-the-absence-of-hd-antigen/. Accessed October 31, 2020.
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