Maternal T cells limit engraftment after in utero hematopoietic cell transplantation in mice
Open Access
- 1 February 2011
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 121 (2), 582-592
- https://doi.org/10.1172/jci44907
Abstract
Transplantation of allogeneic stem cells into the early gestational fetus, a treatment termed in utero hematopoietic cell transplantation (IUHCTx), could potentially overcome the limitations of bone marrow transplants, including graft rejection and the chronic immunosuppression required to prevent rejection. However, clinical use of IUHCTx has been hampered by poor engraftment, possibly due to a host immune response against the graft. Since the fetal immune system is relatively immature, we hypothesized that maternal cells trafficking into the fetus may pose the true barrier to effective IUHCTx. Here, we have demonstrated that there is macrochimerism of maternal leukocytes in the blood of unmanipulated mouse fetuses, with substantial increases in T cell trafficking after IUHCTx. To determine the contribution of these maternal lymphocytes to rejection after IUHCTx, we bred T and/or B cell-deficient mothers to wild-type fathers and performed allogeneic IUHCTx into the immunocompetent fetuses. There was a marked improvement in engraftment if the mother lacked T cells but not B cells, indicating that maternal T cells are the main barrier to engraftment. Furthermore, when the graft was matched to the mother, there was no difference in engraftment between syngeneic and allogeneic fetal recipients. Our study suggests that the clinical success of IUHCTx may be improved by transplanting cells matched to the mother.Keywords
This publication has 49 references indexed in Scilit:
- Maternal alloantibodies induce a postnatal immune response that limits engraftment following in utero hematopoietic cell transplantation in miceJCI Insight, 2009
- Early chimerism threshold predicts sustained engraftment and NK-cell tolerance in prenatal allogeneic chimerasBlood, 2008
- Maternal Alloantigens Promote the Development of Tolerogenic Fetal Regulatory T Cells in UteroScience, 2008
- Tolerance Induction or Sensitization in Mice Exposed to Noninherited Maternal Antigens (NIMA)American Journal of Transplantation, 2008
- Donor major histocompatibility complex class I expression determines the outcome of prenatal transplantationJournal of Pediatric Surgery, 2008
- The human–sheep chimeras as a model for human stem cell mobilization and evaluation of hematopoietic grafts' potentialExperimental Hematology, 2007
- Evidence for an immune barrier after in utero hematopoietic-cell transplantationBlood, 2006
- THE CORRELATION OF PROLONGED SURVIVAL OF MATERNAL SKIN GRAFTS WITH THE PRESENCE OF NATURALLY TRANSFERRED MATERNAL T CELLSTransplantation, 1993
- Mutations in T-cell antigen receptor genes α and β block thymocyte development at different stagesNature, 1992
- RAG-1-deficient mice have no mature B and T lymphocytesCell, 1992