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Gene therapy using adenoviral vector encoding 4-1BBIg gene significantly prolonged murine cardiac allograft survival.
Transpl Immunol. 2006 Aug; 16(2):88-94.TI

Abstract

4-1BB, a member of the tumor necrosis factor (TNF) receptor superfamily, interacts with 4-1BBL expressed on APC and delivers a costimulatory signal for T cell activation and growth. In this study, we investigated the efficacy of an adenoviral vector encoding murine 4-1BB extracellular domain and human IgG1 Fc (Ad4-1BBIg) fusion gene on murine cardiac allograft survival. Abdomen heterotopical heart graft model was performed from Balb/c to C57BL/6 mice. The adenoviral vectors, Ad4-1BBIg or an adenoviral vector containing EGFP gene (AdEGFP), were administered intravenously to recipient animals after cardiac grafting. The cardiac allograft survival was monitored by daily palpation. The serum level of 4-1BBIg and graft histology was assessed. Cytokine profiles in the grafts were detected by RT-PCR. IFN-gamma producing cells in recipient spleen were examined by flow cytometry. 4-1BBIg gene expression was achieved highly level at 72 h after vector injection. The proportion of IFN-gamma producing cells in recipient spleen was significantly reduced after administration of Ad4-1BBIg, compared to the group given AdEGFP or to the untreated control group. Unlike in controls, cardiac allograft expression of mRNA coding for IL-2 and IFN-gamma remained low in the Ad4-1BBIg group. Ad4-1BBIg therapy markedly reduced T cell infiltration into the graft and significantly prolonged recipient survival time (13.5 days), compared to the untreated group (7.5 days) and the AdEGFP-treated group (8.0 days) (P < 0.05). These results indicate that blockade of 4-1BB/4-1BB ligand interactions by Ad4-1BBIg inhibited alloreactive T-cell activation and attenuated T-cell infiltration into the graft, resulting in significant prolongation of murine cardiac allograft survival. Therefore, Ad4-1BBIg may be useful for preventing allograft rejection.

Authors+Show Affiliations

Laboratory of Transplantation, Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16860710

Citation

Huang, Bao-Jun, et al. "Gene Therapy Using Adenoviral Vector Encoding 4-1BBIg Gene Significantly Prolonged Murine Cardiac Allograft Survival." Transplant Immunology, vol. 16, no. 2, 2006, pp. 88-94.
Huang BJ, Yin H, Huang YF, et al. Gene therapy using adenoviral vector encoding 4-1BBIg gene significantly prolonged murine cardiac allograft survival. Transpl Immunol. 2006;16(2):88-94.
Huang, B. J., Yin, H., Huang, Y. F., Xu, J. F., Xiong, P., Feng, W., Zheng, F., Xu, Y., Fang, M., & Gong, F. L. (2006). Gene therapy using adenoviral vector encoding 4-1BBIg gene significantly prolonged murine cardiac allograft survival. Transplant Immunology, 16(2), 88-94.
Huang BJ, et al. Gene Therapy Using Adenoviral Vector Encoding 4-1BBIg Gene Significantly Prolonged Murine Cardiac Allograft Survival. Transpl Immunol. 2006;16(2):88-94. PubMed PMID: 16860710.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gene therapy using adenoviral vector encoding 4-1BBIg gene significantly prolonged murine cardiac allograft survival. AU - Huang,Bao-Jun, AU - Yin,Hui, AU - Huang,Ya-Fei, AU - Xu,Jun-Fa, AU - Xiong,Ping, AU - Feng,Wei, AU - Zheng,Fang, AU - Xu,Yong, AU - Fang,Min, AU - Gong,Fei-Li, Y1 - 2006/04/21/ PY - 2006/02/08/received PY - 2006/03/09/accepted PY - 2006/7/25/pubmed PY - 2006/9/16/medline PY - 2006/7/25/entrez SP - 88 EP - 94 JF - Transplant immunology JO - Transpl Immunol VL - 16 IS - 2 N2 - 4-1BB, a member of the tumor necrosis factor (TNF) receptor superfamily, interacts with 4-1BBL expressed on APC and delivers a costimulatory signal for T cell activation and growth. In this study, we investigated the efficacy of an adenoviral vector encoding murine 4-1BB extracellular domain and human IgG1 Fc (Ad4-1BBIg) fusion gene on murine cardiac allograft survival. Abdomen heterotopical heart graft model was performed from Balb/c to C57BL/6 mice. The adenoviral vectors, Ad4-1BBIg or an adenoviral vector containing EGFP gene (AdEGFP), were administered intravenously to recipient animals after cardiac grafting. The cardiac allograft survival was monitored by daily palpation. The serum level of 4-1BBIg and graft histology was assessed. Cytokine profiles in the grafts were detected by RT-PCR. IFN-gamma producing cells in recipient spleen were examined by flow cytometry. 4-1BBIg gene expression was achieved highly level at 72 h after vector injection. The proportion of IFN-gamma producing cells in recipient spleen was significantly reduced after administration of Ad4-1BBIg, compared to the group given AdEGFP or to the untreated control group. Unlike in controls, cardiac allograft expression of mRNA coding for IL-2 and IFN-gamma remained low in the Ad4-1BBIg group. Ad4-1BBIg therapy markedly reduced T cell infiltration into the graft and significantly prolonged recipient survival time (13.5 days), compared to the untreated group (7.5 days) and the AdEGFP-treated group (8.0 days) (P < 0.05). These results indicate that blockade of 4-1BB/4-1BB ligand interactions by Ad4-1BBIg inhibited alloreactive T-cell activation and attenuated T-cell infiltration into the graft, resulting in significant prolongation of murine cardiac allograft survival. Therefore, Ad4-1BBIg may be useful for preventing allograft rejection. SN - 0966-3274 UR - https://www.unboundmedicine.com/medline/citation/16860710/Gene_therapy_using_adenoviral_vector_encoding_4_1BBIg_gene_significantly_prolonged_murine_cardiac_allograft_survival_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0966-3274(06)00031-1 DB - PRIME DP - Unbound Medicine ER -