| Control of intestinal allograft rejection by FTY720 and costimulation blockade. | |
| | |
MedLine Citation:
|
PMID: 15808565 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
INTRODUCTION: 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. METHODS: 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 microg 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. RESULTS: 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. CONCLUSIONS: FTY720 plus MR1 efficiently delayed intestinal allograft rejection in a mouse model by preventing the infiltration of host lymphocytes, particularly of CD8(+) cells. |
| | |
Authors:
|
S Yan; J I Rodriguez-Barbosa; O Pabst; J H Beckmann; V Brinkmann; R Förster; M W Hoffmann |
Related Documents
:
|
781315 - Intestinal perforation due to fecal impaction after renal transplantation. 18596115 - Adverse renal and metabolic effects associated with oral sodium phosphate bowel prepara... 6440955 - Morphologic study of jejunal mucosal transplants for the replacement of oral mucosa. 1557685 - Net absorption of water, electrolytes, glucose, and folate from the in vivo, neurally i... 16721015 - The role of chronic peritoneal dialysis in the management of the patient with chronic k... 12589535 - Cc-chemokine activation in acute pancreatitis: enhanced release of monocyte chemoattrac... |
Publication Detail:
|
Type: Journal Article |
Journal Detail:
|
Title: Transplantation proceedings Volume: 37 ISSN: 0041-1345 ISO Abbreviation: Transplant. Proc. Publication Date: 2005 Jan-Feb |
Date Detail:
|
Created Date: 2005-04-05 Completed Date: 2005-10-28 Revised Date: 2008-06-05 |
Medline Journal Info:
|
Nlm Unique ID: 0243532 Medline TA: Transplant Proc Country: United States |
Other Details:
|
Languages: eng Pagination: 114-5 Citation Subset: IM |
Affiliation:
|
Medical School of Hannover, Hannover, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Antibodies, Monoclonal / therapeutic use CD40 Ligand / immunology Graft Rejection / prevention & control* Graft Survival / drug effects, immunology* Histocompatibility Testing Immunosuppressive Agents / therapeutic use Intestine, Small / drug effects, immunology, pathology, transplantation* Major Histocompatibility Complex Mice Mice, Inbred C3H Mice, Inbred C57BL Propylene Glycols / therapeutic use* Sphingosine / analogs & derivatives Transplantation, Homologous / immunology* |
| Chemical | |
Reg. No./Substance:
|
0/Antibodies, Monoclonal; 0/Immunosuppressive Agents; 0/Propylene Glycols; 123-78-4/Sphingosine; 147205-72-9/CD40 Ligand; 162359-55-9/fingolimod |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Prolonged administration of FTY720 does not cause renal toxicity in mice.
Next Document: Effect of streptavidin on cardiac allograft prolongation is due to host T-Cell suppression.