Restriction of the T-cell repertoire indicates allo-antigen involvement in chronic transplant rejection

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.