Immunotherapy with nondepleting anti-CD4 monoclonal antibodies but not CD28 antagonists protects islet graft in spontaneously diabetic nod mice from autoimmune destruction and allogeneic and xenogeneic graft rejection
T-cell activation and the subsequent induction of effector functions require not only the recognition of antigen peptides bound to MHC molecules by T-cell receptor (TCR) for antigen but also a costimulatory signal provided by antigen presenting cells. CD4 T-cell activation and function require the C...
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| Veröffentlicht in: | Transplantation 2001-06, Vol.71 (11), p.1656-1665 |
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| creator | Guo, Z Wu, T Kirchhof, N Mital, D Williams, J W Azuma, M Sutherland, D E Hering, B J |
| description | T-cell activation and the subsequent induction of effector functions require not only the recognition of antigen peptides bound to MHC molecules by T-cell receptor (TCR) for antigen but also a costimulatory signal provided by antigen presenting cells. CD4 T-cell activation and function require the CD4 molecule as a coreceptor of TCR. The CD28/B7 pathway is a major costimulatory signal for T-cell activation and differentiation.
The effect of targeting CD4 by nondepleting anti-CD4 monoclonal antibodies (mAbs) versus blocking CD28/B7 by CTLA4Ig, anti-CD80 mAbs, and anti-CD86 mAbs on the prevention of recurrence of autoimmune diabetes after MHC-matched nonobese diabetes-resistant (NOR) islet transplantation in nonobese diabetic (NOD) mice were compared. Whether nondepleting anti-CD4 mAbs prolong allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice were studied. Furthermore, the effect of nondepleting anti-CD4 mAbs combined with CTLA4Ig on allogeneic islet graft survival in NOD mice was investigated.
Recurrence of autoimmune diabetes can be prevented by nondepleting anti-CD4 mAbs. Blocking the CD28/B7 costimulatory pathway by CTLA4Ig or by anti-CD80 mAbs and anti-CD86 mAbs cannot prevent recurrence of autoimmune diabetes after islet transplantation. Short-term treatment with nondepleting anti-CD4 mAbs significantly prolongs allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice. But nondepleting anti-CD4 mAbs combined with CTLA4Ig decreased allogeneic islet graft survival.
Nondepleting anti-CD4 mAbs but not CD28 antagonists protect islet grafts in diabetic NOD mice from autoimmune destruction and allogeneic and xenogeneic graft rejection. The efficacy of nondepleting anti-CD4 mAbs is compromised when it combines with CTLA4Ig. |
| doi_str_mv | 10.1097/00007890-200106150-00027 |
| format | Article |
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The effect of targeting CD4 by nondepleting anti-CD4 monoclonal antibodies (mAbs) versus blocking CD28/B7 by CTLA4Ig, anti-CD80 mAbs, and anti-CD86 mAbs on the prevention of recurrence of autoimmune diabetes after MHC-matched nonobese diabetes-resistant (NOR) islet transplantation in nonobese diabetic (NOD) mice were compared. Whether nondepleting anti-CD4 mAbs prolong allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice were studied. Furthermore, the effect of nondepleting anti-CD4 mAbs combined with CTLA4Ig on allogeneic islet graft survival in NOD mice was investigated.
Recurrence of autoimmune diabetes can be prevented by nondepleting anti-CD4 mAbs. Blocking the CD28/B7 costimulatory pathway by CTLA4Ig or by anti-CD80 mAbs and anti-CD86 mAbs cannot prevent recurrence of autoimmune diabetes after islet transplantation. Short-term treatment with nondepleting anti-CD4 mAbs significantly prolongs allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice. But nondepleting anti-CD4 mAbs combined with CTLA4Ig decreased allogeneic islet graft survival.
Nondepleting anti-CD4 mAbs but not CD28 antagonists protect islet grafts in diabetic NOD mice from autoimmune destruction and allogeneic and xenogeneic graft rejection. The efficacy of nondepleting anti-CD4 mAbs is compromised when it combines with CTLA4Ig.</description><identifier>ISSN: 0041-1337</identifier><identifier>DOI: 10.1097/00007890-200106150-00027</identifier><identifier>PMID: 11435979</identifier><language>eng</language><publisher>United States</publisher><subject>AB7 antigen ; Abatacept ; Animals ; Antibodies, Monoclonal - drug effects ; Antibodies, Monoclonal - therapeutic use ; Antigens, CD ; Antigens, Differentiation - therapeutic use ; Autoimmunity - drug effects ; CD28 antigen ; CD28 Antigens - drug effects ; CD4 antigen ; CD4 Antigens - immunology ; CTLA-4 Antigen ; Diabetes Mellitus - genetics ; Diabetes Mellitus - surgery ; Diabetes Mellitus, Experimental - physiopathology ; Diabetes Mellitus, Experimental - surgery ; Graft Rejection - prevention & control ; Immunoconjugates ; Immunotherapy ; Islets of Langerhans Transplantation - immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, Inbred NOD ; Secondary Prevention ; Survival Analysis ; Swine ; Transplantation, Heterologous - immunology ; Transplantation, Homologous - immunology</subject><ispartof>Transplantation, 2001-06, Vol.71 (11), p.1656-1665</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11435979$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, Z</creatorcontrib><creatorcontrib>Wu, T</creatorcontrib><creatorcontrib>Kirchhof, N</creatorcontrib><creatorcontrib>Mital, D</creatorcontrib><creatorcontrib>Williams, J W</creatorcontrib><creatorcontrib>Azuma, M</creatorcontrib><creatorcontrib>Sutherland, D E</creatorcontrib><creatorcontrib>Hering, B J</creatorcontrib><title>Immunotherapy with nondepleting anti-CD4 monoclonal antibodies but not CD28 antagonists protects islet graft in spontaneously diabetic nod mice from autoimmune destruction and allogeneic and xenogeneic graft rejection</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>T-cell activation and the subsequent induction of effector functions require not only the recognition of antigen peptides bound to MHC molecules by T-cell receptor (TCR) for antigen but also a costimulatory signal provided by antigen presenting cells. CD4 T-cell activation and function require the CD4 molecule as a coreceptor of TCR. The CD28/B7 pathway is a major costimulatory signal for T-cell activation and differentiation.
The effect of targeting CD4 by nondepleting anti-CD4 monoclonal antibodies (mAbs) versus blocking CD28/B7 by CTLA4Ig, anti-CD80 mAbs, and anti-CD86 mAbs on the prevention of recurrence of autoimmune diabetes after MHC-matched nonobese diabetes-resistant (NOR) islet transplantation in nonobese diabetic (NOD) mice were compared. Whether nondepleting anti-CD4 mAbs prolong allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice were studied. Furthermore, the effect of nondepleting anti-CD4 mAbs combined with CTLA4Ig on allogeneic islet graft survival in NOD mice was investigated.
Recurrence of autoimmune diabetes can be prevented by nondepleting anti-CD4 mAbs. Blocking the CD28/B7 costimulatory pathway by CTLA4Ig or by anti-CD80 mAbs and anti-CD86 mAbs cannot prevent recurrence of autoimmune diabetes after islet transplantation. Short-term treatment with nondepleting anti-CD4 mAbs significantly prolongs allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice. But nondepleting anti-CD4 mAbs combined with CTLA4Ig decreased allogeneic islet graft survival.
Nondepleting anti-CD4 mAbs but not CD28 antagonists protect islet grafts in diabetic NOD mice from autoimmune destruction and allogeneic and xenogeneic graft rejection. The efficacy of nondepleting anti-CD4 mAbs is compromised when it combines with CTLA4Ig.</description><subject>AB7 antigen</subject><subject>Abatacept</subject><subject>Animals</subject><subject>Antibodies, Monoclonal - drug effects</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antigens, CD</subject><subject>Antigens, Differentiation - therapeutic use</subject><subject>Autoimmunity - drug effects</subject><subject>CD28 antigen</subject><subject>CD28 Antigens - drug effects</subject><subject>CD4 antigen</subject><subject>CD4 Antigens - immunology</subject><subject>CTLA-4 Antigen</subject><subject>Diabetes Mellitus - genetics</subject><subject>Diabetes Mellitus - surgery</subject><subject>Diabetes Mellitus, Experimental - physiopathology</subject><subject>Diabetes Mellitus, Experimental - surgery</subject><subject>Graft Rejection - prevention & control</subject><subject>Immunoconjugates</subject><subject>Immunotherapy</subject><subject>Islets of Langerhans Transplantation - immunology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred NOD</subject><subject>Secondary Prevention</subject><subject>Survival Analysis</subject><subject>Swine</subject><subject>Transplantation, Heterologous - immunology</subject><subject>Transplantation, Homologous - immunology</subject><issn>0041-1337</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctO5DAQRb0YxGv4hVGtZhfwI4nbS9QMDwlpNuxbTlxpjBw7xI5m-lP5G6ppWONNuY6ub1W5GAPBLwU3-orT0SvDK8m54K1oeEVE6h_slPNaVEIpfcLOcn4h3Citj9mJELVqjDan7O1hHJeYyjPOdtrBP1-eIabocApYfNyCjcVX65saxhRTH1K04YN1yXnM0C2F9AXWN3K153abos8lwzSngj1dfCYn2M52KOAj5CmRKmJactiB87ajOj15OBh9jzDMaQS7lOT3jSE4zGVe-uJTJH8HNoS0xYj0Zp_-x_iVHkrM-IIf6p_saLAh48VnPGdPt3-e1vfV49-7h_X1YzWJRpXK9dxKbuu-a9XgJP1KZ3jbtk4bWwsprRy4sjgoQhzrpjPSmKZrBknY1Oqc_T7Y0sCvCzW7GX3uMYTDjBtNO1K0l2-FYsW15vWKhL8-hUs3ottMsx_tvNt8LU29A3-Pnww</recordid><startdate>20010615</startdate><enddate>20010615</enddate><creator>Guo, Z</creator><creator>Wu, T</creator><creator>Kirchhof, N</creator><creator>Mital, D</creator><creator>Williams, J W</creator><creator>Azuma, M</creator><creator>Sutherland, D E</creator><creator>Hering, B J</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20010615</creationdate><title>Immunotherapy with nondepleting anti-CD4 monoclonal antibodies but not CD28 antagonists protects islet graft in spontaneously diabetic nod mice from autoimmune destruction and allogeneic and xenogeneic graft rejection</title><author>Guo, Z ; Wu, T ; Kirchhof, N ; Mital, D ; Williams, J W ; Azuma, M ; Sutherland, D E ; Hering, B J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p153t-dc0a20a4cb63fd2597b90666d79a4122a2f03aef366d0e45b92995b5f203a943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>AB7 antigen</topic><topic>Abatacept</topic><topic>Animals</topic><topic>Antibodies, Monoclonal - drug effects</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antigens, CD</topic><topic>Antigens, Differentiation - therapeutic use</topic><topic>Autoimmunity - drug effects</topic><topic>CD28 antigen</topic><topic>CD28 Antigens - drug effects</topic><topic>CD4 antigen</topic><topic>CD4 Antigens - immunology</topic><topic>CTLA-4 Antigen</topic><topic>Diabetes Mellitus - genetics</topic><topic>Diabetes Mellitus - surgery</topic><topic>Diabetes Mellitus, Experimental - physiopathology</topic><topic>Diabetes Mellitus, Experimental - surgery</topic><topic>Graft Rejection - prevention & control</topic><topic>Immunoconjugates</topic><topic>Immunotherapy</topic><topic>Islets of Langerhans Transplantation - immunology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred NOD</topic><topic>Secondary Prevention</topic><topic>Survival Analysis</topic><topic>Swine</topic><topic>Transplantation, Heterologous - immunology</topic><topic>Transplantation, Homologous - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Guo, Z</creatorcontrib><creatorcontrib>Wu, T</creatorcontrib><creatorcontrib>Kirchhof, N</creatorcontrib><creatorcontrib>Mital, D</creatorcontrib><creatorcontrib>Williams, J W</creatorcontrib><creatorcontrib>Azuma, M</creatorcontrib><creatorcontrib>Sutherland, D E</creatorcontrib><creatorcontrib>Hering, B J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, Z</au><au>Wu, T</au><au>Kirchhof, N</au><au>Mital, D</au><au>Williams, J W</au><au>Azuma, M</au><au>Sutherland, D E</au><au>Hering, B J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunotherapy with nondepleting anti-CD4 monoclonal antibodies but not CD28 antagonists protects islet graft in spontaneously diabetic nod mice from autoimmune destruction and allogeneic and xenogeneic graft rejection</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2001-06-15</date><risdate>2001</risdate><volume>71</volume><issue>11</issue><spage>1656</spage><epage>1665</epage><pages>1656-1665</pages><issn>0041-1337</issn><abstract>T-cell activation and the subsequent induction of effector functions require not only the recognition of antigen peptides bound to MHC molecules by T-cell receptor (TCR) for antigen but also a costimulatory signal provided by antigen presenting cells. CD4 T-cell activation and function require the CD4 molecule as a coreceptor of TCR. The CD28/B7 pathway is a major costimulatory signal for T-cell activation and differentiation.
The effect of targeting CD4 by nondepleting anti-CD4 monoclonal antibodies (mAbs) versus blocking CD28/B7 by CTLA4Ig, anti-CD80 mAbs, and anti-CD86 mAbs on the prevention of recurrence of autoimmune diabetes after MHC-matched nonobese diabetes-resistant (NOR) islet transplantation in nonobese diabetic (NOD) mice were compared. Whether nondepleting anti-CD4 mAbs prolong allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice were studied. Furthermore, the effect of nondepleting anti-CD4 mAbs combined with CTLA4Ig on allogeneic islet graft survival in NOD mice was investigated.
Recurrence of autoimmune diabetes can be prevented by nondepleting anti-CD4 mAbs. Blocking the CD28/B7 costimulatory pathway by CTLA4Ig or by anti-CD80 mAbs and anti-CD86 mAbs cannot prevent recurrence of autoimmune diabetes after islet transplantation. Short-term treatment with nondepleting anti-CD4 mAbs significantly prolongs allogeneic islet graft survival and xenogeneic pig islet graft survival in diabetic NOD mice. But nondepleting anti-CD4 mAbs combined with CTLA4Ig decreased allogeneic islet graft survival.
Nondepleting anti-CD4 mAbs but not CD28 antagonists protect islet grafts in diabetic NOD mice from autoimmune destruction and allogeneic and xenogeneic graft rejection. The efficacy of nondepleting anti-CD4 mAbs is compromised when it combines with CTLA4Ig.</abstract><cop>United States</cop><pmid>11435979</pmid><doi>10.1097/00007890-200106150-00027</doi><tpages>10</tpages></addata></record> |
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| subjects | AB7 antigen Abatacept Animals Antibodies, Monoclonal - drug effects Antibodies, Monoclonal - therapeutic use Antigens, CD Antigens, Differentiation - therapeutic use Autoimmunity - drug effects CD28 antigen CD28 Antigens - drug effects CD4 antigen CD4 Antigens - immunology CTLA-4 Antigen Diabetes Mellitus - genetics Diabetes Mellitus - surgery Diabetes Mellitus, Experimental - physiopathology Diabetes Mellitus, Experimental - surgery Graft Rejection - prevention & control Immunoconjugates Immunotherapy Islets of Langerhans Transplantation - immunology Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred NOD Secondary Prevention Survival Analysis Swine Transplantation, Heterologous - immunology Transplantation, Homologous - immunology |
| title | Immunotherapy with nondepleting anti-CD4 monoclonal antibodies but not CD28 antagonists protects islet graft in spontaneously diabetic nod mice from autoimmune destruction and allogeneic and xenogeneic graft rejection |
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