title: Reduction of human-to-pig cellular response by alteration of porcine MHC with human HLA DPW0401 exogenes.
abstract: 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 HLA II.
  
  
  METHODS
  With the technique of microinjection, we produced the HLA DPw0401 transgenic pig. The expression of the HLA DPw0401 gene on peripheral blood mononuclear cells (PBMCs) of the transgenic pig was examined by reverse transcriptase-polymerase chain reaction and flow cytometry. The antigenicity of the transgenic HLA DPw0401 molecule was tested by the HLA DPw0401-primed lymphocyte test reagent. The cellular response was analyzed by xenogenic mixed lymphocyte culture.
  
  
  RESULTS
  The mRNA and protein of HLA DPw0401 were expressed in the PBMCs of the transgenic pig. The PBMCs of the HLA transgenic pig induced a stronger cellular reaction to HLA DPw0401-primed lymphocyte test reagents than the nontransgenic littermate pig (n=7, P<0.01). In direct xenogenic mixed lymphocyte culture with responders from HLA DPw0401(+) humans, the PBMCs from the HLA 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 HLA DPw0401 phenotype can be transferred onto porcine cells through the generation of HLA transgenic pigs and make the PBMCs of humans more tolerant to porcine cells.
authors.affiliation: Department of Surgery, National Taiwan University Hospital, 7, Chung Shan South Rd., Taipei, Taiwan, Republic of China.
authors.forename: Jang-Ming
authors.initials: JM
authors.lastname: Lee
authors.forename: Ching-Fu
authors.initials: CF
authors.lastname: Tu
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Yang
authors.forename: Kun-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Kimiyoshi
authors.initials: K
authors.lastname: Tsuji
authors.forename: Meng-Kun
authors.initials: MK
authors.lastname: Tsai
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Chen
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Hu
authors.forename: Rong-Phong
authors.initials: RP
authors.lastname: Hsieh
authors.forename: Hao-Chih
authors.initials: HC
authors.lastname: Tai
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
authors.forename: Chung-Nan
authors.initials: CN
authors.lastname: Weng
authors.forename: Yung-Chie
authors.initials: YC
authors.lastname: Lee
authors.forename: Chun-Jean
authors.initials: CJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D006682:HLA-DP Antigens / Q000235:genetics*; D006801:Humans; D007959:Lymphocyte Culture Test, Mixed; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology*
chemical_list: D006682:HLA-DP Antigens; D012333:RNA, Messenger