title: Highly altered V beta repertoire of T cells infiltrating long-term rejected kidney allografts.
abstract: Chronic rejection represents a major cause of long-term kidney graft loss. T cells that are predominant in long-term rejected kidney allografts (35 +/- 10% of area infiltrate) may thus be instrumental in this phenomenon, which is likely to be dependent on the indirect pathway of allorecognition only. We have analyzed the variations in T cell repertoire usage of the V beta chain at the complementary determining region 3 (CDR3) level in 18 human kidney grafts lost due to chronic rejection. We observed a strongly biased intragraft TCR V beta usage for the majority of V beta families and also a very high percentage (55%) of V beta families exhibiting common and oligoclonal V beta-C beta rearrangements in the grafts of patients with chronic rejection associated with superimposed histologically acute lesions. Furthermore, V beta 8 and V beta 23 families exhibited common and oligoclonal V beta-J beta rearrangements in 4 of 18 patients (22%). Several CDR3 amino acid sequences were found for the common and oligoclonal V beta 8-J beta 1.4 rearrangement. Quantitative PCR showed that biased V beta transcripts were also overexpressed in chronically rejected kidneys with superimposed acute lesions. In contrast, T lymphocytes infiltrating rejected allografts with chronic rejection only showed an unaltered Gaussian-type CDR3 length distribution. This pattern suggests that late graft failure associated with histological lesions restricted to Banff-defined chronic rejection does not involve T cell-mediated injury. Thus, our observation suggests that a limited number of determinants stimulates the recipient immune system in long-term allograft failure. The possibility of a local response against viral or parenchymatous cell-derived determinants is discussed.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 437, "Immunointervention dans les Allo et Xénotransplantations" Nantes, France.
authors.forename: K
authors.initials: K
authors.lastname: Gagne
authors.forename: S
authors.initials: S
authors.lastname: Brouard
authors.forename: M
authors.initials: M
authors.lastname: Giral
authors.forename: F
authors.initials: F
authors.lastname: Sebille
authors.forename: A
authors.initials: A
authors.lastname: Moreau
authors.forename: M
authors.initials: M
authors.lastname: Guillet
authors.forename: J D
authors.initials: JD
authors.lastname: Bignon
authors.forename: B M
authors.initials: BM
authors.lastname: Imbert
authors.forename: M C
authors.initials: MC
authors.lastname: Cuturi
authors.forename: J P
authors.initials: JP
authors.lastname: Soulillou
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002465:Cell Movement / Q000276:immunology*; D002648:Child; D002908:Chronic Disease; D002999:Clone Cells; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D016679:Genome, Viral; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis* / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014158:Transcription, Genetic / Q000276:immunology
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; C075784:T cell receptor Vbeta8