BACKGROUND: The pathogenesis of chronic renal allograft rejection is still speculative. Amongst other factors immune-mediated graft injury is proposed. Since the allo-antigen is specifically recognized by the variable (V) alpha and beta chains of the T-cell receptor, a restricted T-cell repertoire might support the notion of allo-antigen involvement in chronic rejection. METHODS: By the means of semiquantitative polymerase chain reaction the V beta families 1-20 were assessed in allograft biopsies with histologically confirmed chronic and acute rejection. At the same time the V beta repertoire was analyzed in PBMC. RESULT: The intragraft V beta repertoire was limited to 1 to 3 dominant V beta families in chronic and acute rejection. The response was highly individual and did not correlate to the type or degree of HLA mismatches. The T-cell repertoire in PBMC was polyclonal and did not reflect the immune response in the graft. CONCLUSION: The finding of a restricted V beta repertoire in both forms of rejection might indicate an immunological basis not only for acute, but also for ongoing chronic rejection. Tailor-made antibodies against the dominant V beta clones might provide a tool for selective immunosuppression in both entities of rejection targeting only those T cells which were activated by allo-antigens.
BACKGROUND: The pathogenesis of chronic renal allograft rejection is still speculative. Amongst other factors immune-mediated graft injury is proposed. Since the allo-antigen is specifically recognized by the variable (V) alpha and beta chains of the T-cell receptor, a restricted T-cell repertoire might support the notion of allo-antigen involvement in chronic rejection. METHODS: By the means of semiquantitative polymerase chain reaction the V beta families 1-20 were assessed in allograft biopsies with histologically confirmed chronic and acute rejection. At the same time the V beta repertoire was analyzed in PBMC. RESULT: The intragraft V beta repertoire was limited to 1 to 3 dominant V beta families in chronic and acute rejection. The response was highly individual and did not correlate to the type or degree of HLA mismatches. The T-cell repertoire in PBMC was polyclonal and did not reflect the immune response in the graft. CONCLUSION: The finding of a restricted V beta repertoire in both forms of rejection might indicate an immunological basis not only for acute, but also for ongoing chronic rejection. Tailor-made antibodies against the dominant V beta clones might provide a tool for selective immunosuppression in both entities of rejection targeting only those T cells which were activated by allo-antigens.
Authors: B A Yard; M Kooymans-Couthino; T Reterink; P van den Elsen; M E Paape; J A Bruyn; L A van Es; M R Daha; F J van der Woude Journal: Kidney Int Suppl Date: 1993-01 Impact factor: 10.545
Authors: L Struyk; J T Kurnick; G E Hawes; J M van Laar; R Schipper; J R Oksenberg; L Steinman; R R de Vries; F C Breedveld; P van den Elsen Journal: Hum Immunol Date: 1993-08 Impact factor: 2.850
Authors: J R Oksenberg; M A Panzara; A B Begovich; D Mitchell; H A Erlich; R S Murray; R Shimonkevitz; M Sherritt; J Rothbard; C C Bernard; L Steinman Journal: Nature Date: 1993-03-04 Impact factor: 49.962
Authors: G Datema; L M Vaessen; R C Daane; C C Baan; W Weimar; F H Claas; P J van den Elsen Journal: Transplantation Date: 1994-04-15 Impact factor: 4.939