Highly altered V beta repertoire of T cells infiltrating long-term rejected kidney allografts

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 phenomenom, whic h is likely to be dependant 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 ki dney grafts lost due to chronic rejection. We observed a strongly biased in tragraft TCR V beta usage for the majority of V beta families and also a ve ry high percentage (55%) of V beta families exhibiting common and oligoclon al V beta-C beta rearrangements in the grafts of patients with chronic reje ction associated with superimposed histologically acute lesions. Furthermor e, 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 se quences were found for the common and oligoclonal V beta 8-J beta 1.4 rearr angement. Quantitative PCR showed that biased V beta transcripts were also overexpressed in chronically rejected kidneys with superimposed acute lesio ns. In contrast, T lymphocytes infiltrating rejected allografts with chroni c rejection only showed an unaltered Gaussian-type CDR3 length distribution . This pattern suggests that late graft failure associated with histologica l 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 allogra ft failure. The possibility of a local response against viral or parenchyma tous cell-derived determinants is discussed.