title: Evaluation of T-cell receptor repertoires in patients with long-term renal allograft survival.
abstract: The mechanisms underlying long-term acceptance of kidney allografts in humans under minimal or no maintenance immunosuppression are poorly understood. We analyzed the T-cell receptor (TCR) repertoires in circulating T cells of patients with long-term (> or = 9 years) renal allograft survival with (LTS-IS) and without immunosuppression (LTS-NoIS). T cells of LTS patients exhibited strongly altered TCR Vss usage, including an increased frequency of oligoclonality and a decreased frequency of polyclonality. All 3 LTS-NoIS and 12 of 16 LTS-IS patients demonstrated oligoclonality in at least three or more TCR V beta families, and the frequency of oligoclonality in these patients was significantly higher as compared to patients with well-functioning grafts at 3 years (p < 0.005 both), an uncomplicated course during the first year (p < 0.0001, both), acute rejection (p < 0.0001, both), chronic allograft nephropathy at 7 (p < 0.0001, both) or 13 years (p < 0.0001, both), dialysis patients (p < 0.0001, both) or healthy controls (p < 0.0001, both). In contrast to LTS patients, all other studied patient groups exhibited a polyclonal TCR repertoire. Our data indicate that TCR alteration is a common feature of long-term allograft outcome, which might be explained by clonal deletion, exhaustion of alloreactive T cells or predominant expression of particular T-cell subpopulations, such as regulatory T cells.
authors.affiliation: Grupo de Inmunología Celular e Inmunogenética, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Cristiam M
authors.initials: CM
authors.lastname: Alvarez
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
authors.forename: Mabel C
authors.initials: MC
authors.lastname: Giraldo
authors.forename: Steffen
authors.initials: S
authors.lastname: Pelzl
authors.forename: Fabrice
authors.initials: F
authors.lastname: Renner
authors.forename: Rolf
authors.initials: R
authors.lastname: Weimer
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Mario
authors.initials: M
authors.lastname: Arbeláez
authors.forename: Luis F
authors.initials: LF
authors.lastname: García
authors.forename: Caner
authors.initials: C
authors.lastname: Süsal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D022801:Complementarity Determining Regions / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D005260:Female; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006435:Renal Dialysis; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D022801:Complementarity Determining Regions; D011948:Receptors, Antigen, T-Cell