Blog
About

4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      A novel application of cyclosporine A in nonmyeloablative pretransplant host conditioning for allogeneic BMT.

      1 , , ,

      Blood

      Read this article at

      ScienceOpenPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The treatment of mice with anti-CD4 and anti-CD8 monoclonal antibodies (mAbs) on day -5, plus 3 Gy whole body irradiation (WBI) and 7 Gy thymic irradiation (TI) on day 0, allows fully major-histocompatibility-complex-mismatched allogeneic bone marrow engraftment and the induction of immunologic tolerance. TI is required in this model to overcome alloreactivity and possibly to make "space" in the recipient thymus so that lasting central tolerance can be achieved. In addition to suppressing mature T cells in the periphery, Cyclosporine A (CYA) and glucocorticoids have a powerful influence on the thymus. In this study, we evaluated whether the administration of CYA to recipient mice for 12 days prior to bone marrow transplant (BMT), of glucocorticosteroids on the day of BMT, or a combination of both, could create space and overcome alloresistance in the thymus by specifically depleting immature and mature thymocytes prior to BMT. High levels of multilineage donor hematopoietic repopulation and specific transplantation tolerance were achieved in mice treated from days -15 to -3 with CYA (20 mg/kg/d subcutaneously), anti-CD4/CD8 mAbs on day -5, followed by 3 Gy WBI and 15 x 10(6) allogeneic bone marrow cells on day 0. Vbeta analysis suggested a central deletional tolerance mechanism. The same treatment without CYA pretreatment allowed only transient chimerism, without tolerance. Corticosteroid treatment abolished the engraftment-promoting and tolerance-inducing effects of CYA. These results demonstrate a novel pretransplantation-only application of CYA, which facilitates allogeneic marrow engraftment with minimal conditioning, by creating thymic space and/or overcoming intrathymic alloresistance.

          Related collections

          Author and article information

          Journal
          Blood
          Blood
          0006-4971
          0006-4971
          Aug 01 2000
          : 96
          : 3
          Affiliations
          [1 ] Bone Marrow Transplantation Section, Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
          10910938

          Comments

          Comment on this article