The effect of FTY 720 on engraftment in a model of spontaneous allograft acceptance

Further development in organ transplantation requires the utilization of new immunosuppressive drugs that-in addition to being effective against rejection-do not block tolerance. We previously reported that FTY 720, a drug that alters lymphocyte trafficking, has marked anti-rejection properties. We...

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Bibliographic Details
Published in:Transplant international 2003-06, Vol.16 (6), p.383-390
Main Authors: KOSHIBA, Takaaki, VAN DAMME, Boudewijn, PING JI, SEFRIOUI, Hassan, RUTGEERTS, Omer, WAER, Mark, PIRENNE, Jacques
Format: Article
Language:English
Subjects:
Animals
Antibodies, Anti-Idiotypic - immunology
Antibody Formation
Biological and medical sciences
Blood Transfusion
Fingolimod Hydrochloride
Heart Transplantation
Histocompatibility
Immunoglobulin G - immunology
Immunoglobulin M - immunology
Immunomodulators
Immunosuppressive Agents - pharmacology
Intestines - transplantation
Lymphocyte Culture Test, Mixed
Lymphocyte Subsets - drug effects
Lymphocytes - drug effects
Male
Medical sciences
Pharmacology. Drug treatments
Propylene Glycols - pharmacology
Rats
Rats, Inbred Strains
Sphingosine - analogs & derivatives
Tissue Donors
Transplantation Conditioning - methods
Transplantation Tolerance
Transplantation, Heterotopic
Transplantation, Homologous
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Summary:Further development in organ transplantation requires the utilization of new immunosuppressive drugs that-in addition to being effective against rejection-do not block tolerance. We previously reported that FTY 720, a drug that alters lymphocyte trafficking, has marked anti-rejection properties. We now investigate how FTY 720 influences tolerance in a model of graft acceptance by donor-specific blood transfusion (DSBT). Two different transplant models--heart transplantation (Htx) and intestinal transplantation (Itx)--were studied. We performed orthotopic Itx and heterotopic Htx using fully mismatched inbred male RA (RT1(p)) and PVG (RT1(c)) rats as donors and recipients. Tolerance was induced by DSBT on pre-transplant day -12. To test the effect of FTY 720 on DSBT-induced tolerance, we administered FTY 720 orally prior to DSBT. Itx: control rats succumbed to rejection at 18+/-4 days. DSBT alone prolonged survival to 101.9+/-18 days (P
ISSN:0934-0874
1432-2277
DOI:10.1007/s00147-002-0523-9