title: Compromised kidney graft rejection response in Vervet monkeys after withdrawal of immunosuppressants tacrolimus and sirolimus.
abstract: BACKGROUND
  In nonprimates, organ allografts are often not rejected after withdrawal of immunosuppression. In this study, we examined whether such a phenomenon also occurs in primates.
  
  
  METHODS
  Vervet monkeys were transplanted with renal allografts and treated for 60 days with tacrolimus, or tacrolimus plus sirolimus. The drugs were totally withdrawn on day 61. The survival of the monkeys was monitored, and their response to donor- or third party-derived alloantigens was examined in vivo and in vitro.
  
  
  RESULTS
  The majority (80-100%) of the grafts survived for at least additional 30 days with no signs of acute rejection. The compromised rejection is donor-specific, because recipient monkeys failed to reject a donor-derived skin graft, but a third-party skin graft was rejected. In vitro mixed lymphocyte reaction and interleukin-2 production in the mixed lymphocyte reaction between the recipients and their donors or between the recipients and a third party had no discernable patterns, and thus did not reflect the in vivo status of the immune system. Although the recipients could not reject the graft acutely after drug withdrawal, the kidney grafts and the donor-derived skin grafts had pathological findings of chronic rejection.
  
  
  CONCLUSIONS
  The rejection response of the monkeys to an established graft after withdrawal of immunosuppression is compromised. The compromised rejection is specific and is not due to a permanent alteration of the immune system by the initial drug treatment. The allografts are not inert but have low levels of interaction with the recipient immune system.
authors.affiliation: The Research Center, CHUM, University of Montreal, Quebec, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Peng
authors.forename: H
authors.initials: H
authors.lastname: Luo
authors.forename: M
authors.initials: M
authors.lastname: Loubeau
authors.forename: X
authors.initials: X
authors.lastname: Wan
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: S
authors.initials: S
authors.lastname: Qi
authors.forename: M D
authors.initials: MD
authors.lastname: Vu
authors.forename: P
authors.initials: P
authors.lastname: Daloze
authors.forename: W E
authors.initials: WE
authors.lastname: Fitzsimmons
authors.forename: I
authors.initials: I
authors.lastname: Bekersky
authors.forename: J
authors.initials: J
authors.lastname: Peets
authors.forename: S N
authors.initials: SN
authors.lastname: Sehgal
authors.forename: J
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D006084:Graft Rejection / Q000209:etiology* / Q000473:pathology; D006085:Graft Survival; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018664:Interleukin-12 / Q000096:biosynthesis; D016030:Kidney Transplantation / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D020123:Sirolimus / Q000008:administration & dosage* / Q000627:therapeutic use; D016038:Skin Transplantation / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D018664:Interleukin-12; D020123:Sirolimus; D016559:Tacrolimus