title: Microchimerism: tolerance vs. sensitization.
abstract: OBJECTIVE
  The bidirectional exchange of cells, both mature and progenitor types, at the maternal-fetal interface is a common feature of mammalian reproduction. The presence of semiallogeneic cells in a host can have significant immunological effects on transplantation tolerance and rejection. Here, we review recent advances in this area.
  
  
  RESULTS
  Maternal microchimerism (MMc) in blood and various organs was found to be directly correlated with noninherited maternal antigen (NIMA)-specific CD4(+) regulatory T cells (Tregs), in F(1) backcross mice. In humans, MMc induced NIMA-specific FoxP3(+) CD4 Tregs in lymph nodes and spleen of fetuses. Tolerance to NIMA(+) allografts could be predicted in mice by measuring levels of the NIMA-specific Tregs in offspring before transplantation. On the contrary, fetal microchimerism (FMc) in multiparous female mice was largely confined to CD34(+) hematopoietic stem cells (HSCs) and was associated with sensitization rather than Treg induction. The recent discovery of a 'layered' T-cell development in humans whereby fetal HSCs are more likely to produce Tregs than adult HSCs, which may explain why MMc often induces tolerance, whereas FMc tends to induce sensitization.
  
  
  CONCLUSIONS
  Microchimerism may cause tolerance resulting in acceptance of an allograft bearing antigens shared by the microchimeric cells. However, microchimerism may also cause sensitization resulting in rejection. Distinguishing these effects prior to the transplant may revolutionize the field of living-related renal transplantation wherein MMc and FMc can exert a powerful influence on graft outcome.
authors.affiliation: Department of Surgery, University of Wisconsin, Madison, Wisconsin 53792, USA.
authors.forename: Partha
authors.initials: P
authors.lastname: Dutta
authors.forename: William J
authors.initials: WJ
authors.lastname: Burlingham
mesh_terms: D000818:Animals; D017637:Clonal Deletion; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D007519:Isoantigens / Q000276:immunology; D008431:Maternal-Fetal Exchange; D016377:Organ Transplantation / Q000009:adverse effects; D010920:Placenta / Q000276:immunology; D011247:Pregnancy; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018183:Transplantation Chimera; D023001:Transplantation Tolerance; D016896:Treatment Outcome
chemical_list: D007519:Isoantigens