title: Diagnostic value of tolerance-related gene expression measured in the recipient alloantigen-reactive T cell fraction.
abstract: The efficient development of tolerance-inducing therapies and safe reduction of immunosuppression should be supported by early diagnosis and prediction of tolerance in transplantation. Using mouse models of donor-specific tolerance to allogeneic skin and islet grafts we tested whether measurement of tolerance-related gene expression in their alloantigen-reactive peripheral T cell fraction efficiently reflected the tolerance status of recipients. We found that Foxp3, Nrn1, and Klrg1 were preferentially expressed in conditions of tolerance compared with rejection or unmanipulated controls if their expression is measured in CD69(+) T cells prepared from coculture of recipient peripheral T cells and donor antigen-presenting cells. The same pattern of gene expression was observed in recipients grafted with either skin or islets, recipients of different genetic origins, and even those taking immunosuppressive drugs. These findings suggest that the expression of tolerance-related genes in the alloantigen-reactive T cell fraction could be used to detect tolerance in the clinic.
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Dong-Gyun
authors.initials: DG
authors.lastname: Lim
authors.forename: Youn-Hee
authors.initials: YH
authors.lastname: Park
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Seong-Hee
authors.initials: SH
authors.lastname: Jeong
authors.forename: Song-Cheol
authors.initials: SC
authors.lastname: Kim
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D016572:Cyclosporine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology / Q000502:physiology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D020123:Sirolimus / Q000494:pharmacology; D016038:Skin Transplantation / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D007519:Isoantigens; D016572:Cyclosporine; D020123:Sirolimus
keywords: APC; Alloreactive T cells; CsA; DST; Gene expression; Immune monitoring; Tolerance; antigen-presenting cell; cyclosporine A; donor-specific transfusion; mPD; methylprednisolone; qRT-PCR; quantitative reverse-transcription polymerase chain reaction