Rejection of the transplanted uterus is suppressed by cyclosporine A in a semi-allogeneic mouse model

Hum Reprod. 2007 Feb;22(2):372-9. doi: 10.1093/humrep/del410. Epub 2006 Oct 24.

Abstract

Background: A mouse uterus transplantation model has previously been developed for studies of various aspects of uterine transplantation, which in the future may be used as treatment for uterine infertility. The aim of the study was to evaluate the effect of the immunosuppressant cyclosporine A (CyA) on the rejection of the allotransplanted uterus in the mouse.

Methods: C57BL/6 mice were recipients of uteri from F1 hybrids (C57BL/6 x CBA/ca). Transplanted mice received vehicle (control, n=5), 10 or 20 mg/kg/day of CyA (CyA10, n=5 and CyA20, n=5). Untreated F1 hybrids with syngeneic transplants (n=3) were negative controls. On day 10 post-transplantation, the grafted uteri were examined, and biopsies were taken for histology and quantification of T cells.

Results: Histology analysis revealed necrosis of the uterine transplants in controls and to a lesser extent in the CyA groups. Apoptosis and inflammation was prominent in grafts from the CyA10 group but suppressed in the CyA20 group. A similar increase of CD4+ cells was seen in all groups, whereas the number of CD8+ cells was higher (P < 0.05) in the two allogeneic groups receiving CyA compared with the allogeneic vehicle group.

Conclusions: CyA treatment clearly delays the progress of rejection of grafted uteri but is insufficient to suppress T cell infiltration. Interestingly, the number of CD8+ cells was higher in groups receiving CyA, possibly reflecting a CyA-dependent depression of activation-induced cell death (AICD) of cytotoxic T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / cytology
  • Cyclosporine / administration & dosage
  • Cyclosporine / therapeutic use*
  • Female
  • Graft Rejection / pathology
  • Graft Rejection / prevention & control*
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Uterus / pathology
  • Uterus / transplantation*

Substances

  • Immunosuppressive Agents
  • Cyclosporine