Reduction of human-to-pig cellular response by alteration of porcine MHC with human HLA DPW0401 exogenes

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

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12 Citations (Scopus)

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, PΑ0.01). 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.

Original languageEnglish
Pages (from-to)193-197
Number of pages5
JournalTransplantation
Volume73
Issue number2
Publication statusPublished - Jan 27 2002
Externally publishedYes

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Swine
Blood Cells
Lymphocytes
Heterografts
HLA-DPW0401 antigen
Heterologous Transplantation
Microinjections
Reverse Transcriptase Polymerase Chain Reaction
Blood Vessels
Flow Cytometry
T-Lymphocytes
Transplants
Phenotype
Messenger RNA

ASJC Scopus subject areas

  • Transplantation

Cite this

Lee, J. M., Tu, C. F., Yang, P. W., Lee, K. H., Tsuji, K., Tsai, M. K., ... Lee, C. J. (2002). Reduction of human-to-pig cellular response by alteration of porcine MHC with human HLA DPW0401 exogenes. Transplantation, 73(2), 193-197.

Reduction of human-to-pig cellular response by alteration of porcine MHC with human HLA DPW0401 exogenes. / Lee, Jang Ming; Tu, Ching Fu; Yang, Pei Wen; Lee, Kun Hsiung; Tsuji, Kimiyoshi; Tsai, Meng Kun; Chen, Robert J.; Hu, Chung Yi; Hsieh, Rong Phong; Tai, Hao Chih; Chiang, Bor Luen; Weng, Chung Nan; Lee, Yung Chie; Lee, Chun Jean.

In: Transplantation, Vol. 73, No. 2, 27.01.2002, p. 193-197.

Research output: Contribution to journalArticle

Lee, JM, Tu, CF, Yang, PW, Lee, KH, Tsuji, K, Tsai, MK, Chen, RJ, Hu, CY, Hsieh, RP, Tai, HC, Chiang, BL, Weng, CN, Lee, YC & Lee, CJ 2002, 'Reduction of human-to-pig cellular response by alteration of porcine MHC with human HLA DPW0401 exogenes', Transplantation, vol. 73, no. 2, pp. 193-197.
Lee JM, Tu CF, Yang PW, Lee KH, Tsuji K, Tsai MK et al. Reduction of human-to-pig cellular response by alteration of porcine MHC with human HLA DPW0401 exogenes. Transplantation. 2002 Jan 27;73(2):193-197.
Lee, Jang Ming ; Tu, Ching Fu ; Yang, Pei Wen ; Lee, Kun Hsiung ; Tsuji, Kimiyoshi ; Tsai, Meng Kun ; Chen, Robert J. ; Hu, Chung Yi ; Hsieh, Rong Phong ; Tai, Hao Chih ; Chiang, Bor Luen ; Weng, Chung Nan ; Lee, Yung Chie ; Lee, Chun Jean. / Reduction of human-to-pig cellular response by alteration of porcine MHC with human HLA DPW0401 exogenes. In: Transplantation. 2002 ; Vol. 73, No. 2. pp. 193-197.
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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, PΑ0.01). 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.",
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AU - Lee, Jang Ming

AU - Tu, Ching Fu

AU - Yang, Pei Wen

AU - Lee, Kun Hsiung

AU - Tsuji, Kimiyoshi

AU - Tsai, Meng Kun

AU - Chen, Robert J.

AU - Hu, Chung Yi

AU - Hsieh, Rong Phong

AU - Tai, Hao Chih

AU - Chiang, Bor Luen

AU - Weng, Chung Nan

AU - Lee, Yung Chie

AU - Lee, Chun Jean

PY - 2002/1/27

Y1 - 2002/1/27

N2 - 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, PΑ0.01). 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.

AB - 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, PΑ0.01). 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.

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