Reduction of Human-to-Pig Cellular Response by Alteration of Porcine MHC with Human HLA DPW0401 Exogenes

10.30047/JGMB.200603.0004

Jang-Ming Lee；Ching-Fu Tu；Pei-Wen Yang；Kun-Hsiung Lee；Kimiyoshi Tsuji；Meng-Kun Tsai；Robert J Chen；Chung-Yi Hu；Rong-Phong Hsieh；Hao-Chih Tai；Bor-Luen Chiang；Chung-Nan Weng；Yung-Chie Lee；Chun-Jean Lee

Journal of Genetics and Molecular Biology

17卷1期（2006 / 03 / 01）

11 - 19

英文

Background. In pig-to-human discordant xenotransplantation, the xenograft can be rejected by a formidable human xenogenic T-cell response, even if the graft has gone through hyperacute rejection or delayed xenograft rejection (acute vascular rejection). We therefore examined, in this study, whether the human-to-pig cellular response could be attenuated through the generation of a transgenic pig for human IIIA H. Methods. With the technique of microinjection, we produced the HILA DPw0401 transgenic pig. The expression of the HILA DPw0401 gene on peripheral blood mononuclear cells (PBMCs) of the transgenic pig was examined by reverse transcriptasepolymerase chain reaction and flow cytometry. The antigenicity of the transgenic HIA DPw0401 molecule was tested by the EIIA DPw0401-primed lymphocyte test reagent. The cellular response was analyzed by xenogenic mixed lymphocyte culture. Results. The mRNA and protein of ELLA DPw0401 were expressed in the PBMCs of the transgenic pig. The PBMCs of the HIA transgenic pig induced a stronger cellular reaction to HILA DPw0401-primed lymphocyte test reagents than the nontransgenic littermate pig (n=7, P＜0.01). In direct xenogenic mixed lymphocyte culture with responders from HIA DPw04Ol(+) humans, the PBMCs from the HIA DPw0401 transgenic pig, as compared with those from the normal pig, induced a lower degree of xenogenic cellular response to human PBMCs (n=4, P=0.08). Conclusions. Our preliminary data demonstrated the possibility that the human HIA DPw0401 phenotype can be transferred onto porcine cells through the generation of HILA transgenic pigs and make the PBMCs of humans more tolerant to porcine cells.