title: Renal transplant patients show variations in their self-reactive repertoires: a serial study.
abstract: We addressed the question of whether allo-transplantation (Tx) induces breakdown of tolerance to self-antigens or alteration of the autoreactive T cell repertoire in humans. The serial variation of T cell autoreactivity was studied in the peripheral blood of 12 renal transplant patients, by autologous limiting dilution assay and autologous mixed lymphocyte reaction. Ten of 12 patients presented a positive response in autologous peripheral blood mononuclear cells in the post-Tx period, in contrast to four of 12 patients before Tx (P = 0.038). Multi-hit kinetics was found in 57% of the assays analyzed, indicating frequent regulatory control of the autologous response. Quantitative analysis performed in eight patients showed an increase in precursor frequency at >1 year post-Tx in five patients. These data indicate that autoreactivity increases or develops following Tx, in humans. Post-Tx events such as alloreactivity, infections or immunosuppression could interfere with the balance of autoreactive and regulatory cells, leading to changes in the T cell repertoires to self-antigens and eventually breakdown of self-tolerance. Further investigation is needed to elucidate whether post-Tx autoreactivity contributes to rejection, plays a regulatory role over alloreactivity or both, at separate times.
authors.affiliation: Heart Institute (InCor) and Division of Renal Transplantation, Hospital of Clinics, University of São Paulo Medical School, Av. Dr Enéas de Carvalho Aguiar 500, 3, São Paulo 05403-000, Brazil.
authors.forename: K
authors.initials: K
authors.lastname: Portugal
authors.forename: I
authors.initials: I
authors.lastname: Dozmorov
authors.forename: I
authors.initials: I
authors.lastname: Sidorov
authors.forename: I
authors.initials: I
authors.lastname: Marrero
authors.forename: J A
authors.initials: JA
authors.lastname: Fonseca
authors.forename: M
authors.initials: M
authors.lastname: Spadafora-Ferreira
authors.forename: J
authors.initials: J
authors.lastname: Kalil
authors.forename: V
authors.initials: V
authors.lastname: Coelho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000276:immunology; D001803:Blood Transfusion; D002675:Child, Preschool; D002999:Clone Cells; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D017634:Self Tolerance / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D023001:Transplantation Tolerance / Q000276:immunology; D014184:Transplantation, Homologous
chemical_list: D001324:Autoantigens; D010835:Phytohemagglutinins