title: Regulatory T cells are not predictive of outcomes in a nonhuman primate model of vascularized composite allotransplantation.
abstract: BACKGROUND
  T regulatory cells (Tregs) have been associated with prolonged allograft survival and tolerance across a wide variety of species and organ types. We used our nonhuman primate model of facial vascularized composite allotransplantation (VCA) to study the association of Tregs with graft outcomes.
  
  
  METHODS
  We quantified Tregs in peripheral blood and allograft biopsies from nonhuman primates after heterotopic partial facial segment allotransplantation from major histocompatibility complex class I-mismatched donors using flow cytometry and immunohistochemistry. Immunosuppression consisted of tacrolimus and mycophenolate mofetil without induction or depletional therapies. Circulating and graft skin Treg values were compared with graft outcomes and with histologic grade from concurrent biopsies.
  
  
  RESULTS
  Treg proportion in peripheral blood ranged from 0.156% to 9.00% with a mean of 3.34%±0.22%. FoxP3 staining was observed in 3 of 29 graft biopsies. Median circulating Treg value did not predict time to Banff grade II rejection (hazard ratio, 0.9; confidence interval, 0.4-2.2) or graft loss (hazard ratio, 0.5; confidence interval, 0.01-5.3). Animals that experienced rejection did not have significantly different peripheral blood or graft skin Treg values from those that did not. Biopsy specimens with grade I or II rejection were more likely to contain Tregs (25% vs. 0%; P=0.044) despite no difference in concurrent circulating Tregs (3.56% vs. 3.36%; P=0.704).
  
  
  CONCLUSIONS
  These findings in a clinically relevant model suggest that Tregs may have limited prognostic value with standard immunosuppressive protocols used in VCA. Further studies are necessary to determine the specific role of Tregs in VCA and any role of Treg monitoring in clinical practice.
authors.affiliation: Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Brazio
authors.forename: Raghava B
authors.initials: RB
authors.lastname: Munivenkatappa
authors.forename: Branko
authors.initials: B
authors.lastname: Bojovic
authors.forename: Jinny S
authors.initials: JS
authors.lastname: Ha
authors.forename: Emile N
authors.initials: EN
authors.lastname: Brown
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Hess
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Bartlett
authors.forename: Eduardo D
authors.initials: ED
authors.lastname: Rodriguez
authors.forename: Rolf N
authors.initials: RN
authors.lastname: Barth
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008252:Macaca fascicularis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D063986:Vascularized Composite Allotransplantation / Q000009:adverse effects*
chemical_list: D007166:Immunosuppressive Agents