Engineering an ectopic thymus in the lymph node to induce central tolerance and long-term allograft acceptance (TRAN3P.896)

Abstract

Abstract Background: Allogeneic transplant rejection is one of the major problems plaguing the field of organ transplants. Our previous studies have established the lymph node as a functional site for thymus transplant. In this study, we hypothesized that conditioning transplant recipients with thymic cells immune-matched to the donor will induce long-term acceptance of a subsequent allograft. Methods: We transplanted Balb/c-GFP thymuses into the lymph nodes of FAH-/- mice on a 129sv background. After 6 weeks, the animals were challenged with donor-matched skin grafts or hepatocyte transfer and monitored for long-term allograft acceptance. We also assessed tolerance induction by performing mixed lymphocyte reaction assays (MLR), immunostaining of native and ectopic thymus, as well as thymic dendritic cell (tDC)-T cell co-cultures. Results: Mice receiving thymus transplants successfully accepted subsequent allografts long-term. MLR reactions demonstrated Balb/c-specific tolerance in these mice. We also observed migration of cells (mostly tDCs) from the ectopic to the native thymus. tDC-T cell co-cultures revealed that migrating DCs from the ectopic as well as native thymus were instrumental in generating the increased numbers of Tregs observed in recipient mice. Conclusion: We were able to achieve long-term allograft acceptance in mice receiving thymic transplants, which was possibly mediated by the increased Treg induction associated with cross-talk between the two thymuses.