Control of intestinal allograft rejection by FTY720 and costimulation blockade
The clinical application of small bowel transplantation (SBTx) is hampered by its pronounced immunogenicity. In this study we examined the effects of the novel immunosuppressant FTY720 and costimulation blockade by an anti-CD40L mAb (MR-1) in a stringent mouse model of SBTx. SBTx was performed in mi...
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| Veröffentlicht in: | Transplantation proceedings 2005, Vol.37 (1), p.114-115 |
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| creator | Yan, S. Rodriguez-Barbosa, J.I. Pabst, O. Beckmann, J.H. Brinkmann, V. Förster, R. Hoffmann, M.W. |
| description | The clinical application of small bowel transplantation (SBTx) is hampered by
its pronounced immunogenicity. In this study we examined the effects of the novel
immunosuppressant FTY720 and costimulation blockade by an anti-CD40L mAb (MR-1) in
a stringent mouse model of SBTx.
SBTx was performed in mice with a full MHC mismatch (donors: C3H=H-2
k;
recipients: C57BL/6=H-2
b). Recipients were divided into four groups: 1, untreated group; 2,
MR1 monotherapy (500 μg IV on days 0, 2, 4, and 7); 3, FTY720 monotherapy (1 mg/kg body
weight PO for 14 consecutive days after transplantation); 4, FTY720 plus MR1–treated group.
Graft rejection grades were assessed by H&E staining. Graft mesenteric lymph nodes (MLNs),
Peyer's patches (PPs), as well as intraepithelial lymphocytes (IELs) and lamina propria
lymphocytes (LPLs) were analyzed by flow cytometry and three-color immunofluorescence
staining.
Neither FTY720 nor MR1 monotherapy was efficient in preventing the rejection of
mouse intestinal allografts, whereas FTY720 plus MR1 profoundly inhibited the rejection
response at the 14th posttransplant day. The infiltration of host lymphocytes was reduced in
graft MLNs, PPs, IELs, and LPLs by FTY720 therapy. FTY720 plus MR1 inhibited host
CD8
+ T-cell infiltration in graft LPLs when compared with grafts treated with FTY720 only.
Additionally, two subpopulations, CD11b
+high Gr1
− and CD11b
+intermediate Gr1
+ cells, were
decreased in FTY720-treated grafts.
FTY720 plus MR1 efficiently delayed intestinal allograft rejection in a mouse
model by preventing the infiltration of host lymphocytes, particularly of CD8
+ cells. |
| doi_str_mv | 10.1016/j.transproceed.2004.12.089 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67708324</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0041134504015283</els_id><sourcerecordid>67708324</sourcerecordid><originalsourceid>FETCH-LOGICAL-c378t-bf7b2fa2132c4bd79087ff97482aa0a30178404f733700fc9157e4ae5b7115283</originalsourceid><addsrcrecordid>eNqNkDtPwzAUhS0EoqXwF1DEwJbgRxI7bKhQQKpgKQOT5Tg2cnDiYidI_fe4SoUYma6uzrmP8wFwhWCGICpv2mzwog9b76RSTYYhzDOEM8iqIzBHjJIUl5gcg3kUUIpIXszAWQgtjD3OySmYoYJBVpTFHLwsXT94ZxOnE9MPKgymFzYR1roPL_SQeNUqORjXJ_UuWW3eKYaJ6JtEumjtRismzTr5KRp1Dk60sEFdHOoCvK0eNsundP36-Ly8W6eSUDaktaY11gIjgmVeN7SCjGpd0ZxhIaAgEFGWw1xTQiiEWlaooCoXqqgpQgVmZAGup70RwtcYv-adCVJZK3rlxsBLSiEjMewC3E5G6V0IXmm-9aYTfscR5HuavOV_afI9TY4wjzTj8OXhylh3UfsdPeCLhvvJoGLWb6M8D9KoXqrG-EiNN878584PeIaMsw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67708324</pqid></control><display><type>article</type><title>Control of intestinal allograft rejection by FTY720 and costimulation blockade</title><source>MEDLINE</source><source>Elsevier ScienceDirect</source><creator>Yan, S. ; Rodriguez-Barbosa, J.I. ; Pabst, O. ; Beckmann, J.H. ; Brinkmann, V. ; Förster, R. ; Hoffmann, M.W.</creator><creatorcontrib>Yan, S. ; Rodriguez-Barbosa, J.I. ; Pabst, O. ; Beckmann, J.H. ; Brinkmann, V. ; Förster, R. ; Hoffmann, M.W.</creatorcontrib><description>The clinical application of small bowel transplantation (SBTx) is hampered by
its pronounced immunogenicity. In this study we examined the effects of the novel
immunosuppressant FTY720 and costimulation blockade by an anti-CD40L mAb (MR-1) in
a stringent mouse model of SBTx.
SBTx was performed in mice with a full MHC mismatch (donors: C3H=H-2
k;
recipients: C57BL/6=H-2
b). Recipients were divided into four groups: 1, untreated group; 2,
MR1 monotherapy (500 μg IV on days 0, 2, 4, and 7); 3, FTY720 monotherapy (1 mg/kg body
weight PO for 14 consecutive days after transplantation); 4, FTY720 plus MR1–treated group.
Graft rejection grades were assessed by H&E staining. Graft mesenteric lymph nodes (MLNs),
Peyer's patches (PPs), as well as intraepithelial lymphocytes (IELs) and lamina propria
lymphocytes (LPLs) were analyzed by flow cytometry and three-color immunofluorescence
staining.
Neither FTY720 nor MR1 monotherapy was efficient in preventing the rejection of
mouse intestinal allografts, whereas FTY720 plus MR1 profoundly inhibited the rejection
response at the 14th posttransplant day. The infiltration of host lymphocytes was reduced in
graft MLNs, PPs, IELs, and LPLs by FTY720 therapy. FTY720 plus MR1 inhibited host
CD8
+ T-cell infiltration in graft LPLs when compared with grafts treated with FTY720 only.
Additionally, two subpopulations, CD11b
+high Gr1
− and CD11b
+intermediate Gr1
+ cells, were
decreased in FTY720-treated grafts.
FTY720 plus MR1 efficiently delayed intestinal allograft rejection in a mouse
model by preventing the infiltration of host lymphocytes, particularly of CD8
+ cells.</description><identifier>ISSN: 0041-1345</identifier><identifier>EISSN: 1873-2623</identifier><identifier>DOI: 10.1016/j.transproceed.2004.12.089</identifier><identifier>PMID: 15808565</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Antibodies, Monoclonal - therapeutic use ; CD40 Ligand - immunology ; Fingolimod Hydrochloride ; Graft Rejection - prevention & control ; Graft Survival - drug effects ; Graft Survival - immunology ; Histocompatibility Testing ; Immunosuppressive Agents - therapeutic use ; Intestine, Small - drug effects ; Intestine, Small - immunology ; Intestine, Small - pathology ; Intestine, Small - transplantation ; Major Histocompatibility Complex ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Propylene Glycols - therapeutic use ; Sphingosine - analogs & derivatives ; Transplantation, Homologous - immunology</subject><ispartof>Transplantation proceedings, 2005, Vol.37 (1), p.114-115</ispartof><rights>2005 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-bf7b2fa2132c4bd79087ff97482aa0a30178404f733700fc9157e4ae5b7115283</citedby><cites>FETCH-LOGICAL-c378t-bf7b2fa2132c4bd79087ff97482aa0a30178404f733700fc9157e4ae5b7115283</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.transproceed.2004.12.089$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,4025,27928,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15808565$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yan, S.</creatorcontrib><creatorcontrib>Rodriguez-Barbosa, J.I.</creatorcontrib><creatorcontrib>Pabst, O.</creatorcontrib><creatorcontrib>Beckmann, J.H.</creatorcontrib><creatorcontrib>Brinkmann, V.</creatorcontrib><creatorcontrib>Förster, R.</creatorcontrib><creatorcontrib>Hoffmann, M.W.</creatorcontrib><title>Control of intestinal allograft rejection by FTY720 and costimulation blockade</title><title>Transplantation proceedings</title><addtitle>Transplant Proc</addtitle><description>The clinical application of small bowel transplantation (SBTx) is hampered by
its pronounced immunogenicity. In this study we examined the effects of the novel
immunosuppressant FTY720 and costimulation blockade by an anti-CD40L mAb (MR-1) in
a stringent mouse model of SBTx.
SBTx was performed in mice with a full MHC mismatch (donors: C3H=H-2
k;
recipients: C57BL/6=H-2
b). Recipients were divided into four groups: 1, untreated group; 2,
MR1 monotherapy (500 μg IV on days 0, 2, 4, and 7); 3, FTY720 monotherapy (1 mg/kg body
weight PO for 14 consecutive days after transplantation); 4, FTY720 plus MR1–treated group.
Graft rejection grades were assessed by H&E staining. Graft mesenteric lymph nodes (MLNs),
Peyer's patches (PPs), as well as intraepithelial lymphocytes (IELs) and lamina propria
lymphocytes (LPLs) were analyzed by flow cytometry and three-color immunofluorescence
staining.
Neither FTY720 nor MR1 monotherapy was efficient in preventing the rejection of
mouse intestinal allografts, whereas FTY720 plus MR1 profoundly inhibited the rejection
response at the 14th posttransplant day. The infiltration of host lymphocytes was reduced in
graft MLNs, PPs, IELs, and LPLs by FTY720 therapy. FTY720 plus MR1 inhibited host
CD8
+ T-cell infiltration in graft LPLs when compared with grafts treated with FTY720 only.
Additionally, two subpopulations, CD11b
+high Gr1
− and CD11b
+intermediate Gr1
+ cells, were
decreased in FTY720-treated grafts.
FTY720 plus MR1 efficiently delayed intestinal allograft rejection in a mouse
model by preventing the infiltration of host lymphocytes, particularly of CD8
+ cells.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>CD40 Ligand - immunology</subject><subject>Fingolimod Hydrochloride</subject><subject>Graft Rejection - prevention & control</subject><subject>Graft Survival - drug effects</subject><subject>Graft Survival - immunology</subject><subject>Histocompatibility Testing</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Intestine, Small - drug effects</subject><subject>Intestine, Small - immunology</subject><subject>Intestine, Small - pathology</subject><subject>Intestine, Small - transplantation</subject><subject>Major Histocompatibility Complex</subject><subject>Mice</subject><subject>Mice, Inbred C3H</subject><subject>Mice, Inbred C57BL</subject><subject>Propylene Glycols - therapeutic use</subject><subject>Sphingosine - analogs & derivatives</subject><subject>Transplantation, Homologous - immunology</subject><issn>0041-1345</issn><issn>1873-2623</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkDtPwzAUhS0EoqXwF1DEwJbgRxI7bKhQQKpgKQOT5Tg2cnDiYidI_fe4SoUYma6uzrmP8wFwhWCGICpv2mzwog9b76RSTYYhzDOEM8iqIzBHjJIUl5gcg3kUUIpIXszAWQgtjD3OySmYoYJBVpTFHLwsXT94ZxOnE9MPKgymFzYR1roPL_SQeNUqORjXJ_UuWW3eKYaJ6JtEumjtRismzTr5KRp1Dk60sEFdHOoCvK0eNsundP36-Ly8W6eSUDaktaY11gIjgmVeN7SCjGpd0ZxhIaAgEFGWw1xTQiiEWlaooCoXqqgpQgVmZAGup70RwtcYv-adCVJZK3rlxsBLSiEjMewC3E5G6V0IXmm-9aYTfscR5HuavOV_afI9TY4wjzTj8OXhylh3UfsdPeCLhvvJoGLWb6M8D9KoXqrG-EiNN878584PeIaMsw</recordid><startdate>2005</startdate><enddate>2005</enddate><creator>Yan, S.</creator><creator>Rodriguez-Barbosa, J.I.</creator><creator>Pabst, O.</creator><creator>Beckmann, J.H.</creator><creator>Brinkmann, V.</creator><creator>Förster, R.</creator><creator>Hoffmann, M.W.</creator><general>Elsevier Inc</general><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></search><sort><creationdate>2005</creationdate><title>Control of intestinal allograft rejection by FTY720 and costimulation blockade</title><author>Yan, S. ; Rodriguez-Barbosa, J.I. ; Pabst, O. ; Beckmann, J.H. ; Brinkmann, V. ; Förster, R. ; Hoffmann, M.W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-bf7b2fa2132c4bd79087ff97482aa0a30178404f733700fc9157e4ae5b7115283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>CD40 Ligand - immunology</topic><topic>Fingolimod Hydrochloride</topic><topic>Graft Rejection - prevention & control</topic><topic>Graft Survival - drug effects</topic><topic>Graft Survival - immunology</topic><topic>Histocompatibility Testing</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Intestine, Small - drug effects</topic><topic>Intestine, Small - immunology</topic><topic>Intestine, Small - pathology</topic><topic>Intestine, Small - transplantation</topic><topic>Major Histocompatibility Complex</topic><topic>Mice</topic><topic>Mice, Inbred C3H</topic><topic>Mice, Inbred C57BL</topic><topic>Propylene Glycols - therapeutic use</topic><topic>Sphingosine - analogs & derivatives</topic><topic>Transplantation, Homologous - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yan, S.</creatorcontrib><creatorcontrib>Rodriguez-Barbosa, J.I.</creatorcontrib><creatorcontrib>Pabst, O.</creatorcontrib><creatorcontrib>Beckmann, J.H.</creatorcontrib><creatorcontrib>Brinkmann, V.</creatorcontrib><creatorcontrib>Förster, R.</creatorcontrib><creatorcontrib>Hoffmann, M.W.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Transplantation proceedings</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yan, S.</au><au>Rodriguez-Barbosa, J.I.</au><au>Pabst, O.</au><au>Beckmann, J.H.</au><au>Brinkmann, V.</au><au>Förster, R.</au><au>Hoffmann, M.W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Control of intestinal allograft rejection by FTY720 and costimulation blockade</atitle><jtitle>Transplantation proceedings</jtitle><addtitle>Transplant Proc</addtitle><date>2005</date><risdate>2005</risdate><volume>37</volume><issue>1</issue><spage>114</spage><epage>115</epage><pages>114-115</pages><issn>0041-1345</issn><eissn>1873-2623</eissn><abstract>The clinical application of small bowel transplantation (SBTx) is hampered by
its pronounced immunogenicity. In this study we examined the effects of the novel
immunosuppressant FTY720 and costimulation blockade by an anti-CD40L mAb (MR-1) in
a stringent mouse model of SBTx.
SBTx was performed in mice with a full MHC mismatch (donors: C3H=H-2
k;
recipients: C57BL/6=H-2
b). Recipients were divided into four groups: 1, untreated group; 2,
MR1 monotherapy (500 μg IV on days 0, 2, 4, and 7); 3, FTY720 monotherapy (1 mg/kg body
weight PO for 14 consecutive days after transplantation); 4, FTY720 plus MR1–treated group.
Graft rejection grades were assessed by H&E staining. Graft mesenteric lymph nodes (MLNs),
Peyer's patches (PPs), as well as intraepithelial lymphocytes (IELs) and lamina propria
lymphocytes (LPLs) were analyzed by flow cytometry and three-color immunofluorescence
staining.
Neither FTY720 nor MR1 monotherapy was efficient in preventing the rejection of
mouse intestinal allografts, whereas FTY720 plus MR1 profoundly inhibited the rejection
response at the 14th posttransplant day. The infiltration of host lymphocytes was reduced in
graft MLNs, PPs, IELs, and LPLs by FTY720 therapy. FTY720 plus MR1 inhibited host
CD8
+ T-cell infiltration in graft LPLs when compared with grafts treated with FTY720 only.
Additionally, two subpopulations, CD11b
+high Gr1
− and CD11b
+intermediate Gr1
+ cells, were
decreased in FTY720-treated grafts.
FTY720 plus MR1 efficiently delayed intestinal allograft rejection in a mouse
model by preventing the infiltration of host lymphocytes, particularly of CD8
+ cells.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15808565</pmid><doi>10.1016/j.transproceed.2004.12.089</doi><tpages>2</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0041-1345 |
| ispartof | Transplantation proceedings, 2005, Vol.37 (1), p.114-115 |
| issn | 0041-1345 1873-2623 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect |
| subjects | Animals Antibodies, Monoclonal - therapeutic use CD40 Ligand - immunology Fingolimod Hydrochloride Graft Rejection - prevention & control Graft Survival - drug effects Graft Survival - immunology Histocompatibility Testing Immunosuppressive Agents - therapeutic use Intestine, Small - drug effects Intestine, Small - immunology Intestine, Small - pathology Intestine, Small - transplantation Major Histocompatibility Complex Mice Mice, Inbred C3H Mice, Inbred C57BL Propylene Glycols - therapeutic use Sphingosine - analogs & derivatives Transplantation, Homologous - immunology |
| title | Control of intestinal allograft rejection by FTY720 and costimulation blockade |
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