CD4 and CD8 monoclonal antibody therapy: Strategies to prolong renal allograft survival in the dog
The value of CD4 and CD8 monoclonal antibody therapy in tolerance induction has been demonstrated in rodent transplant models. In this paper the immunosuppressive potential of CD4 and CD8 monoclonal antibodies for dog renal allografts was evaluated as a preliminary to tolerogenic studies in this lar...
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| Veröffentlicht in: | British journal of surgery 1993-11, Vol.80 (11), p.1389-1392 |
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| container_title | British journal of surgery |
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| creator | Watson, C. J. E. Cobbold, S. P. Davies, H. F. S. Rebello, P. R. U. B. Waldmann, H. Calne, R. Y. Metcalfe, S. M. |
| description | The value of CD4 and CD8 monoclonal antibody therapy in tolerance induction has been demonstrated in rodent transplant models. In this paper the immunosuppressive potential of CD4 and CD8 monoclonal antibodies for dog renal allografts was evaluated as a preliminary to tolerogenic studies in this large animal model. Monoclonal antibodies were given for a maximum of 10 days after transplantation. Therapy was stopped prematurely following adverse reactions associated with the recipient developing an antibody response against the foreign (rat) therapeutic monoclonal antibody. Blood trough levels of CD4 and CD8 antibodies indicated that saturating doses were achieved. Although neither CD4 nor CD8 alone prolonged allograft survival (rejection by day 7), combination of CD4 and CD8 antibodies resulted in good graft function for a median of 14 days. The effect of removing circulating T lymphocytes was also assessed using a lytic Thy‐1 monoclonal antibody. Alone Thy‐1 had little effect but, when combined with CD4, the median allograft survival time was increased to 15.5 days. Reduction of the number of circulating T lymphocytes appears complementary to blockade of CD4 for immunosuppression, while blockade of CD4 combined with removal of CD8 also favours allograft survival. |
| doi_str_mv | 10.1002/bjs.1800801111 |
| format | Article |
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J. E. ; Cobbold, S. P. ; Davies, H. F. S. ; Rebello, P. R. U. B. ; Waldmann, H. ; Calne, R. Y. ; Metcalfe, S. M.</creator><creatorcontrib>Watson, C. J. E. ; Cobbold, S. P. ; Davies, H. F. S. ; Rebello, P. R. U. B. ; Waldmann, H. ; Calne, R. Y. ; Metcalfe, S. M.</creatorcontrib><description>The value of CD4 and CD8 monoclonal antibody therapy in tolerance induction has been demonstrated in rodent transplant models. In this paper the immunosuppressive potential of CD4 and CD8 monoclonal antibodies for dog renal allografts was evaluated as a preliminary to tolerogenic studies in this large animal model. Monoclonal antibodies were given for a maximum of 10 days after transplantation. Therapy was stopped prematurely following adverse reactions associated with the recipient developing an antibody response against the foreign (rat) therapeutic monoclonal antibody. Blood trough levels of CD4 and CD8 antibodies indicated that saturating doses were achieved. Although neither CD4 nor CD8 alone prolonged allograft survival (rejection by day 7), combination of CD4 and CD8 antibodies resulted in good graft function for a median of 14 days. The effect of removing circulating T lymphocytes was also assessed using a lytic Thy‐1 monoclonal antibody. Alone Thy‐1 had little effect but, when combined with CD4, the median allograft survival time was increased to 15.5 days. Reduction of the number of circulating T lymphocytes appears complementary to blockade of CD4 for immunosuppression, while blockade of CD4 combined with removal of CD8 also favours allograft survival.</description><identifier>ISSN: 0007-1323</identifier><identifier>EISSN: 1365-2168</identifier><identifier>DOI: 10.1002/bjs.1800801111</identifier><identifier>PMID: 8252344</identifier><identifier>CODEN: BJSUAM</identifier><language>eng</language><publisher>Bristol: John Wiley & Sons, Ltd</publisher><subject>Animals ; Antibodies, Monoclonal - therapeutic use ; Biological and medical sciences ; CD4 Antigens - immunology ; CD8 Antigens - immunology ; Dogs ; Female ; Graft Survival - immunology ; Immune Tolerance ; Kidney Transplantation - immunology ; Leukocyte Count ; Male ; Medical sciences ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the urinary system ; T-Lymphocytes ; Time Factors ; Transplantation, Homologous</subject><ispartof>British journal of surgery, 1993-11, Vol.80 (11), p.1389-1392</ispartof><rights>Copyright © 1993 British Journal of Surgery Society Ltd.</rights><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3681-3d1f80b3995993b8f026ddd079b9a9331c296b2859438f4640bc98b60b01f7183</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fbjs.1800801111$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fbjs.1800801111$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>309,310,314,776,780,785,786,1411,23909,23910,25118,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3823667$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8252344$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Watson, C. J. E.</creatorcontrib><creatorcontrib>Cobbold, S. P.</creatorcontrib><creatorcontrib>Davies, H. F. S.</creatorcontrib><creatorcontrib>Rebello, P. R. U. B.</creatorcontrib><creatorcontrib>Waldmann, H.</creatorcontrib><creatorcontrib>Calne, R. Y.</creatorcontrib><creatorcontrib>Metcalfe, S. M.</creatorcontrib><title>CD4 and CD8 monoclonal antibody therapy: Strategies to prolong renal allograft survival in the dog</title><title>British journal of surgery</title><addtitle>Br J Surg</addtitle><description>The value of CD4 and CD8 monoclonal antibody therapy in tolerance induction has been demonstrated in rodent transplant models. In this paper the immunosuppressive potential of CD4 and CD8 monoclonal antibodies for dog renal allografts was evaluated as a preliminary to tolerogenic studies in this large animal model. Monoclonal antibodies were given for a maximum of 10 days after transplantation. Therapy was stopped prematurely following adverse reactions associated with the recipient developing an antibody response against the foreign (rat) therapeutic monoclonal antibody. Blood trough levels of CD4 and CD8 antibodies indicated that saturating doses were achieved. Although neither CD4 nor CD8 alone prolonged allograft survival (rejection by day 7), combination of CD4 and CD8 antibodies resulted in good graft function for a median of 14 days. The effect of removing circulating T lymphocytes was also assessed using a lytic Thy‐1 monoclonal antibody. Alone Thy‐1 had little effect but, when combined with CD4, the median allograft survival time was increased to 15.5 days. Reduction of the number of circulating T lymphocytes appears complementary to blockade of CD4 for immunosuppression, while blockade of CD4 combined with removal of CD8 also favours allograft survival.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>CD4 Antigens - immunology</subject><subject>CD8 Antigens - immunology</subject><subject>Dogs</subject><subject>Female</subject><subject>Graft Survival - immunology</subject><subject>Immune Tolerance</subject><subject>Kidney Transplantation - immunology</subject><subject>Leukocyte Count</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the urinary system</subject><subject>T-Lymphocytes</subject><subject>Time Factors</subject><subject>Transplantation, Homologous</subject><issn>0007-1323</issn><issn>1365-2168</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkUFvEzEQhS0EKqFw5YbkA-pty4y967W5QVpaqgoOBSFxsexdb3Bx1sHelObf12mi1Bd75n1vNPIj5C3CKQKwD_Y2n6IEkIDlPCMz5KKpGAr5nMwAoK2QM_6SvMr5FgA5NOyIHEnWMF7XM2LnZzU1Y0_nZ5Iu4xi7EEcTSmvyNvYbOv1xyaw2H-nNlMzkFt5lOkW6SrGAC5rcIx1CXCQzTDSv052_Ky0_bq20j4vX5MVgQnZv9vcx-fnl_Mf8srr-fvF1_um66riQWPEeBwmWK9Uoxa0cgIm-76FVVhnFOXZMCctko2ouh1rUYDslrQALOLQo-TE52c0tu_1buzzppc-dC8GMLq6zbgUCU_UWfLcH13bper1KfmnSRu8_pejv97rJnQlDMmPn8wHjknEh2oKpHfbfB7c5yAh6G4wuweinYPTnq5unqnirndfnyd0fvCb91WVy2-hf3y40skuFv6E8-ANxxo5L</recordid><startdate>199311</startdate><enddate>199311</enddate><creator>Watson, C. J. E.</creator><creator>Cobbold, S. P.</creator><creator>Davies, H. F. S.</creator><creator>Rebello, P. R. U. B.</creator><creator>Waldmann, H.</creator><creator>Calne, R. Y.</creator><creator>Metcalfe, S. M.</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>199311</creationdate><title>CD4 and CD8 monoclonal antibody therapy: Strategies to prolong renal allograft survival in the dog</title><author>Watson, C. J. E. ; Cobbold, S. P. ; Davies, H. F. S. ; Rebello, P. R. U. B. ; Waldmann, H. ; Calne, R. Y. ; Metcalfe, S. 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Graft diseases</topic><topic>Surgery of the urinary system</topic><topic>T-Lymphocytes</topic><topic>Time Factors</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Watson, C. J. E.</creatorcontrib><creatorcontrib>Cobbold, S. P.</creatorcontrib><creatorcontrib>Davies, H. F. S.</creatorcontrib><creatorcontrib>Rebello, P. R. U. B.</creatorcontrib><creatorcontrib>Waldmann, H.</creatorcontrib><creatorcontrib>Calne, R. Y.</creatorcontrib><creatorcontrib>Metcalfe, S. 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M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD4 and CD8 monoclonal antibody therapy: Strategies to prolong renal allograft survival in the dog</atitle><jtitle>British journal of surgery</jtitle><addtitle>Br J Surg</addtitle><date>1993-11</date><risdate>1993</risdate><volume>80</volume><issue>11</issue><spage>1389</spage><epage>1392</epage><pages>1389-1392</pages><issn>0007-1323</issn><eissn>1365-2168</eissn><coden>BJSUAM</coden><abstract>The value of CD4 and CD8 monoclonal antibody therapy in tolerance induction has been demonstrated in rodent transplant models. In this paper the immunosuppressive potential of CD4 and CD8 monoclonal antibodies for dog renal allografts was evaluated as a preliminary to tolerogenic studies in this large animal model. Monoclonal antibodies were given for a maximum of 10 days after transplantation. Therapy was stopped prematurely following adverse reactions associated with the recipient developing an antibody response against the foreign (rat) therapeutic monoclonal antibody. Blood trough levels of CD4 and CD8 antibodies indicated that saturating doses were achieved. Although neither CD4 nor CD8 alone prolonged allograft survival (rejection by day 7), combination of CD4 and CD8 antibodies resulted in good graft function for a median of 14 days. The effect of removing circulating T lymphocytes was also assessed using a lytic Thy‐1 monoclonal antibody. Alone Thy‐1 had little effect but, when combined with CD4, the median allograft survival time was increased to 15.5 days. Reduction of the number of circulating T lymphocytes appears complementary to blockade of CD4 for immunosuppression, while blockade of CD4 combined with removal of CD8 also favours allograft survival.</abstract><cop>Bristol</cop><pub>John Wiley & Sons, Ltd</pub><pmid>8252344</pmid><doi>10.1002/bjs.1800801111</doi><tpages>4</tpages></addata></record> |
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| subjects | Animals Antibodies, Monoclonal - therapeutic use Biological and medical sciences CD4 Antigens - immunology CD8 Antigens - immunology Dogs Female Graft Survival - immunology Immune Tolerance Kidney Transplantation - immunology Leukocyte Count Male Medical sciences Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the urinary system T-Lymphocytes Time Factors Transplantation, Homologous |
| title | CD4 and CD8 monoclonal antibody therapy: Strategies to prolong renal allograft survival in the dog |
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