Potent Antirheumatic Activity of a New DNA Vaccine Targeted to B7-2/CD28 Costimulatory Signaling Pathway in Autoimmune Arthritis
Rheumatoid arthritis is a proinflammatory autoimmune disease attributed to failure of both CD4(+)CD25(+) regulatory T (Tr) and CD8(+)CD28(-) suppressor T (Ts) cells to control autoreactive CD4(+)CD28(+) Th1 (Th1) and autoantibody-producing B cells. Here we show a single intramuscular injection of ou...
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| Veröffentlicht in: | Human gene therapy 2011, Vol.22 (1), p.65-76 |
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| container_title | Human gene therapy |
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| creator | Xue, Hong Liang, Fei Liu, Nan Song, Xinqiang Yuan, Fang Luo, Yuan Zhao, Xiao Long, Juan Sun, Yuying Xi, Yongzhi |
| description | Rheumatoid arthritis is a proinflammatory autoimmune disease attributed to failure of both CD4(+)CD25(+) regulatory T (Tr) and CD8(+)CD28(-) suppressor T (Ts) cells to control autoreactive CD4(+)CD28(+) Th1 (Th1) and autoantibody-producing B cells. Here we show a single intramuscular injection of our novel targeted DNA vaccine encoding Pseudomonas exotoxin A and costimulatory molecule B7-2 without autoantigens in a collagen-induced arthritis model simultaneously increased Tr and Ts cells and selectively decreased autoreactive Th1 cells. The vaccine induced a shift from Th1 to Th2 and Th3 cellular and cytokine profiles and a decrease in CD4(+)/CD8(+) cell ratios. Importantly, the vaccine showed potent antirheumatic activity by clinical and other examinations such as X-ray, histopathology, and anti-type II collagen IgG levels and was comparable to methotrexate, the current "gold standard" treatment. As an effective stimulator of both Tr and Ts cells and a specific suppressor of autoreactive Th1 cells, this vaccine is a promising therapeutic approach for rheumatoid arthritis. |
| doi_str_mv | 10.1089/hum.2010.110 |
| format | Article |
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Here we show a single intramuscular injection of our novel targeted DNA vaccine encoding Pseudomonas exotoxin A and costimulatory molecule B7-2 without autoantigens in a collagen-induced arthritis model simultaneously increased Tr and Ts cells and selectively decreased autoreactive Th1 cells. The vaccine induced a shift from Th1 to Th2 and Th3 cellular and cytokine profiles and a decrease in CD4(+)/CD8(+) cell ratios. Importantly, the vaccine showed potent antirheumatic activity by clinical and other examinations such as X-ray, histopathology, and anti-type II collagen IgG levels and was comparable to methotrexate, the current "gold standard" treatment. As an effective stimulator of both Tr and Ts cells and a specific suppressor of autoreactive Th1 cells, this vaccine is a promising therapeutic approach for rheumatoid arthritis.</description><identifier>ISSN: 1043-0342</identifier><identifier>EISSN: 1557-7422</identifier><identifier>DOI: 10.1089/hum.2010.110</identifier><identifier>PMID: 20695769</identifier><identifier>CODEN: HGTHE3</identifier><language>eng</language><publisher>Larchmont, NY: Liebert</publisher><subject><![CDATA[ADP Ribose Transferases - administration & dosage ; ADP Ribose Transferases - immunology ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Antirheumatic Agents - immunology ; Antirheumatic Agents - metabolism ; Applied cell therapy and gene therapy ; Arthritis, Experimental - immunology ; Arthritis, Rheumatoid - immunology ; Arthritis, Rheumatoid - prevention & control ; B7-2 Antigen - administration & dosage ; B7-2 Antigen - immunology ; Bacterial Toxins - administration & dosage ; Bacterial Toxins - immunology ; Biological and medical sciences ; Biotechnology ; CD28 Antigens - immunology ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Cell physiology ; Cytokines - immunology ; Exotoxins - administration & dosage ; Exotoxins - immunology ; Female ; Fundamental and applied biological sciences. Psychology ; Gene therapy ; Health. Pharmaceutical industry ; Industrial applications and implications. Economical aspects ; Medical sciences ; Molecular and cellular biology ; Pseudomonas ; Pseudomonas aeruginosa Exotoxin A ; Rats ; Rats, Wistar ; Signal Transduction ; T-Lymphocytes, Regulatory - immunology ; Th1 Cells - immunology ; Th2 Cells - immunology ; Transfusions. Complications. Transfusion reactions. 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Here we show a single intramuscular injection of our novel targeted DNA vaccine encoding Pseudomonas exotoxin A and costimulatory molecule B7-2 without autoantigens in a collagen-induced arthritis model simultaneously increased Tr and Ts cells and selectively decreased autoreactive Th1 cells. The vaccine induced a shift from Th1 to Th2 and Th3 cellular and cytokine profiles and a decrease in CD4(+)/CD8(+) cell ratios. Importantly, the vaccine showed potent antirheumatic activity by clinical and other examinations such as X-ray, histopathology, and anti-type II collagen IgG levels and was comparable to methotrexate, the current "gold standard" treatment. As an effective stimulator of both Tr and Ts cells and a specific suppressor of autoreactive Th1 cells, this vaccine is a promising therapeutic approach for rheumatoid arthritis.</description><subject>ADP Ribose Transferases - administration & dosage</subject><subject>ADP Ribose Transferases - immunology</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Antirheumatic Agents - immunology</subject><subject>Antirheumatic Agents - metabolism</subject><subject>Applied cell therapy and gene therapy</subject><subject>Arthritis, Experimental - immunology</subject><subject>Arthritis, Rheumatoid - immunology</subject><subject>Arthritis, Rheumatoid - prevention & control</subject><subject>B7-2 Antigen - administration & dosage</subject><subject>B7-2 Antigen - immunology</subject><subject>Bacterial Toxins - administration & dosage</subject><subject>Bacterial Toxins - immunology</subject><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>CD28 Antigens - immunology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cell physiology</subject><subject>Cytokines - immunology</subject><subject>Exotoxins - administration & dosage</subject><subject>Exotoxins - immunology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene therapy</subject><subject>Health. Pharmaceutical industry</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Medical sciences</subject><subject>Molecular and cellular biology</subject><subject>Pseudomonas</subject><subject>Pseudomonas aeruginosa Exotoxin A</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Signal Transduction</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Th1 Cells - immunology</subject><subject>Th2 Cells - immunology</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Vaccines, DNA - immunology</subject><subject>Vaccines, DNA - metabolism</subject><subject>Virulence Factors - administration & dosage</subject><subject>Virulence Factors - immunology</subject><issn>1043-0342</issn><issn>1557-7422</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1P3DAQQC1EBZRy44x8Qb004I_465guLVRCFKm018jrjHeNkhhsp2hv_enNim177GlmpDfv8hA6peSCEm0u19Nwwcj2omQPHVEhVKVqxvbnndS8Irxmh-htzo-EUC6kOkCHjEgjlDRH6Nd9LDAW3IwlpDVMgy3B4caV8DOUDY4eW3wHL_jqrsE_rHNhBPxg0woKdLhE_FFV7HJxxTRexFzCMPW2xLTB38JqtH0YV_jelvWL3eAw4mYqMQzDNDuaVNYplJDfoTfe9hlOdvMYff_86WFxU91-vf6yaG4rxwUrlYZaa8ol9UvwSnZLozvtoaaELomgxBomTUeAUyW0kNpo7alxToKqQXnDj9H7V-9Tis8T5NIOITvoeztCnHI7Pyk9f8v_k7U0hBmzdX54JV2KOSfw7VMKg02blpJ2G6ed47TbOO0cZ8bPduJpOUD3F_5TYwbOd4DNzvY-2dGF_I_jhhqiBP8NGv6WZw</recordid><startdate>2011</startdate><enddate>2011</enddate><creator>Xue, Hong</creator><creator>Liang, Fei</creator><creator>Liu, Nan</creator><creator>Song, Xinqiang</creator><creator>Yuan, Fang</creator><creator>Luo, Yuan</creator><creator>Zhao, Xiao</creator><creator>Long, Juan</creator><creator>Sun, Yuying</creator><creator>Xi, Yongzhi</creator><general>Liebert</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>7T5</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope></search><sort><creationdate>2011</creationdate><title>Potent Antirheumatic Activity of a New DNA Vaccine Targeted to B7-2/CD28 Costimulatory Signaling Pathway in Autoimmune Arthritis</title><author>Xue, Hong ; Liang, Fei ; Liu, Nan ; Song, Xinqiang ; Yuan, Fang ; Luo, Yuan ; Zhao, Xiao ; Long, Juan ; Sun, Yuying ; Xi, Yongzhi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c352t-8e4881361fbef76db98d8fe4101b0510a9269d0e31758568988f19cc6e74e7f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>ADP Ribose Transferases - administration & dosage</topic><topic>ADP Ribose Transferases - immunology</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Antirheumatic Agents - immunology</topic><topic>Antirheumatic Agents - metabolism</topic><topic>Applied cell therapy and gene therapy</topic><topic>Arthritis, Experimental - immunology</topic><topic>Arthritis, Rheumatoid - immunology</topic><topic>Arthritis, Rheumatoid - prevention & control</topic><topic>B7-2 Antigen - administration & dosage</topic><topic>B7-2 Antigen - immunology</topic><topic>Bacterial Toxins - administration & dosage</topic><topic>Bacterial Toxins - immunology</topic><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>CD28 Antigens - immunology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cell physiology</topic><topic>Cytokines - immunology</topic><topic>Exotoxins - administration & dosage</topic><topic>Exotoxins - immunology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene therapy</topic><topic>Health. Pharmaceutical industry</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Medical sciences</topic><topic>Molecular and cellular biology</topic><topic>Pseudomonas</topic><topic>Pseudomonas aeruginosa Exotoxin A</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Signal Transduction</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Th1 Cells - immunology</topic><topic>Th2 Cells - immunology</topic><topic>Transfusions. Complications. Transfusion reactions. 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Here we show a single intramuscular injection of our novel targeted DNA vaccine encoding Pseudomonas exotoxin A and costimulatory molecule B7-2 without autoantigens in a collagen-induced arthritis model simultaneously increased Tr and Ts cells and selectively decreased autoreactive Th1 cells. The vaccine induced a shift from Th1 to Th2 and Th3 cellular and cytokine profiles and a decrease in CD4(+)/CD8(+) cell ratios. Importantly, the vaccine showed potent antirheumatic activity by clinical and other examinations such as X-ray, histopathology, and anti-type II collagen IgG levels and was comparable to methotrexate, the current "gold standard" treatment. As an effective stimulator of both Tr and Ts cells and a specific suppressor of autoreactive Th1 cells, this vaccine is a promising therapeutic approach for rheumatoid arthritis.</abstract><cop>Larchmont, NY</cop><pub>Liebert</pub><pmid>20695769</pmid><doi>10.1089/hum.2010.110</doi><tpages>12</tpages></addata></record> |
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| subjects | ADP Ribose Transferases - administration & dosage ADP Ribose Transferases - immunology Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Antirheumatic Agents - immunology Antirheumatic Agents - metabolism Applied cell therapy and gene therapy Arthritis, Experimental - immunology Arthritis, Rheumatoid - immunology Arthritis, Rheumatoid - prevention & control B7-2 Antigen - administration & dosage B7-2 Antigen - immunology Bacterial Toxins - administration & dosage Bacterial Toxins - immunology Biological and medical sciences Biotechnology CD28 Antigens - immunology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell physiology Cytokines - immunology Exotoxins - administration & dosage Exotoxins - immunology Female Fundamental and applied biological sciences. Psychology Gene therapy Health. Pharmaceutical industry Industrial applications and implications. Economical aspects Medical sciences Molecular and cellular biology Pseudomonas Pseudomonas aeruginosa Exotoxin A Rats Rats, Wistar Signal Transduction T-Lymphocytes, Regulatory - immunology Th1 Cells - immunology Th2 Cells - immunology Transfusions. Complications. Transfusion reactions. Cell and gene therapy Vaccines, DNA - immunology Vaccines, DNA - metabolism Virulence Factors - administration & dosage Virulence Factors - immunology |
| title | Potent Antirheumatic Activity of a New DNA Vaccine Targeted to B7-2/CD28 Costimulatory Signaling Pathway in Autoimmune Arthritis |
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