PMID: 7519216Aug 15, 1994Paper

FK506 inhibits graft-versus-host disease and bone marrow graft rejection in murine recipients of MHC disparate donor grafts by interfering with mature peripheral T cell expansion post-transplantation

The Journal of Immunology : Official Journal of the American Association of Immunologists
B R BlazarD A Vallera

Abstract

FK506 was evaluated as the sole graft-vs-host disease (GVHD) preventive agent in murine recipients of fully allogeneic donor grafts. FK506 (36 mg/kg given as a suspension on days 0 through 13, then three times per wk through day 29 post-bone marrow transplantation (BMT)) reproducibly led to 50 to 90% of FK506-treated recipients surviving a 60- to 103-day observation period. High doses of cyclosporin A did not protect mice from lethal GVHD. A kinetic study performed in mice that received FK506 demonstrated that mature donor CD3+, CD4+, and CD8+ T cells in the spleen were each reduced by > or = 64%, as compared with vehicle-treated control mice, although this effect was short lived. Thymic reconstitution studies revealed a remarkable decrease in mature CD4+ cells and cells expressing the activation Ag, CD69. In contrast, less mature CD4+8+ thymocytes were not reduced significantly and total thymocyte numbers were only marginally decreased. The fact that peripheral reconstitution of CD4+8- or CD8+4- T cells was impaired significantly at this time indicated that FK506 had a major effect on thymic maturation and/or thymic emigration. In two models specifically designed to study alloengraftment, recipients of pan-T cell-depleted (TCD...Continue Reading

Related Concepts

Related Feeds

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.