title: Donor reactive regulatory T cells.
abstract: OBJECTIVE
  Donor reactive regulatory T cells (Treg) play an important role in tolerance induction and maintenance in experimental transplant models. In this review we focus on the formation of the donor reactive Treg pool and explore the potential of these cells for therapeutic application in clinical transplantation.
  
  
  RESULTS
  Donor reactive Treg can arise by both conversion of alloreactive nonregulatory cells and expansion of naturally occurring Treg (nTreg) cross-reactive with donor alloantigen but the quantitative contribution of each of these pathways is at present unclear. However, the fact that donor reactive Treg can be driven both in vivo and ex vivo by alloantigen challenge of nonregulatory precursors is encouraging as it demonstrates that the functional potential of these cells for use in clinical transplantation will not be limited by fortuitous cross-reactivity between nTreg and donor alloantigens. Treg can be generated in vivo by transplantation or alloantigen challenge in combination with Treg-permissive immunosuppression, or ex vivo by phenotypic selection or by polyclonal or antigen-specific stimulation. A number of ex-vivo protocols exist for the enrichment of Treg in the laboratory and in many cases these cells have demonstrable function both in vitro and in relevant graft-versus-host disease (GVHD) or organ transplant models. The challenge now is to understand the clinical opportunities and limitations that these populations present.
  
  
  CONCLUSIONS
  Combined with appropriate immunosuppression, Treg generated/expanded in vivo or ex vivo may hold the final key to operational tolerance in clinical setting.
authors.affiliation: Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Gang
authors.initials: G
authors.lastname: Feng
authors.forename: Thomas
authors.initials: T
authors.lastname: Chan
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Wood
authors.forename: Andrew
authors.initials: A
authors.lastname: Bushell
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D016377:Organ Transplantation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation*; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D023001:Transplantation Tolerance; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D007519:Isoantigens; D007371:Interferon-gamma