Combined donor leucocyte administration and immunosuppressive drug treatment for survival of rat heart allografts

Transplant Immunology
Marcel den DulkG Alex Bishop

Abstract

Donor leucocytes (DL) play an important role in rat liver transplant tolerance and their postoperative administration can convert rejection to tolerance. They appear to induce early activation, altered patterns of infiltration and death of recipient alloreactive T cells. The ability of immunosuppressive drugs to combine with DL administration was examined in a rat heart transplant model. Immediately after PVG to DA heterotopic heart transplantation, 6 x 10(7) spleen DL were injected. Cyclosporine A (CsA), 1.5 mg/kg/day, or methotrexate (MTX), 0.1 or 0.2 mg/kg/day, were given from day (d) 0 to d4 (early) or from d3 to d7 (delayed). Castanospermine (CAST) was administered from d0 to d7 at 100 or 300 mg/kg/day. In a separate experiment, transplanted hearts and recipient spleens were collected from treatment groups for analysis of infiltrate and cytokine mRNA expression. Delayed treatment with CsA or early treatment with MTX but not CAST combined with DL to result in prolonged graft survival. Recipients treated with DL and delayed CsA had a reduced level of intra-graft interleukin (IL)-2, interferon (IFN)-gamma, IL-4, and IL-4R mRNA expression and reduced infiltrate compared to DL alone. Early MTX plus DL led to almost complete inh...Continue Reading

References

Jan 1, 1993·Transplant Immunology·T T PizarroL A Piccinini
Feb 1, 1997·Transplantation Proceedings·C RicordiA G Tzakis
Jul 17, 1998·The Journal of Clinical Investigation·L GenestierJ P Revillard
Oct 20, 1998·Transplant Immunology·C J CiesielskiL A Piccinini
Mar 10, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·H KaminskiP Merville

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