title: Human allograft acceptance is associated with immune regulation.
abstract: The ultimate goal of transplantation is drug-free allograft acceptance, which is rarely encountered in transplant recipients. Using a novel human-to-mouse "trans vivo" delayed-type hypersensitivity assay, we assessed donor-reactive cell-mediated immune responses in kidney and liver transplant patients, four of whom discontinued all immunosuppression. One of these subjects (J.B.) rejected his graft after 7 years of stable function, while the others (D.S., R.D., M.L.) continue to have excellent graft function 5, 28, and 4 years after the cessation of immunosuppression. PBMCs from J.B. exhibited strong responses to both donor and recall antigens whereas PBMCs from patients D.S., R.D., and M.L. responded strongly to recall, but not donor, antigens. Furthermore, when donor and recall antigens were colocalized, the recall response in these three patients was inhibited. This donor antigen-linked nonresponsiveness was observed in four other patients who are still maintained on immunosuppression. The weakness of donor-reactive DTH responses in these patients is due to donor alloantigen-triggered regulation that relies on either TGF-beta or IL-10. In D.S., regulation is triggered by a single donor HLA Class I antigen, either in membrane-bound or soluble form. This demonstrates that allograft acceptance in humans is associated with an immune regulation pattern, which may be useful in the diagnosis and/or monitoring of transplant patients for allograft acceptance.
authors.affiliation: Department of Surgery, Ohio State University, Columbus, Ohio, USA. vanbuskirk.1@osu.edu
authors.forename: A M
authors.initials: AM
authors.lastname: VanBuskirk
authors.forename: W J
authors.initials: WJ
authors.lastname: Burlingham
authors.forename: E
authors.initials: E
authors.lastname: Jankowska-Gan
authors.forename: T
authors.initials: T
authors.lastname: Chin
authors.forename: S
authors.initials: S
authors.lastname: Kusaka
authors.forename: F
authors.initials: F
authors.lastname: Geissler
authors.forename: R P
authors.initials: RP
authors.lastname: Pelletier
authors.forename: C G
authors.initials: CG
authors.lastname: Orosz
mesh_terms: D000818:Animals; D015234:HLA-A Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000209:etiology*; D016753:Interleukin-10 / Q000502:physiology; D016030:Kidney Transplantation / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D011817:Rabbits; D016212:Transforming Growth Factor beta / Q000502:physiology; D014184:Transplantation, Homologous
chemical_list: D015234:HLA-A Antigens; D006684:HLA-DR Antigens; D016212:Transforming Growth Factor beta; D016753:Interleukin-10