Barth C, Von Menges A, Zanker B, Lammerding P, Stachowski J, Baldamus C A
Medizinische Klinik IV, University Hospital, Cologne, Germany.
Kidney Int. 1996 Dec;50(6):2020-6. doi: 10.1038/ki.1996.524.
Allo-MHC specific antigen recognition might not only be involved in acute, but also in chronic rejection. The clonotypic specificity of the T-cell receptor to recognize all-MHC is located in the variable (V) alpha and beta chain. A restricted T-cell receptor repertoire could support an immunological basis for chronic rejection. The novel feature of this study is that V beta repertoire was assessed in ongoing chronic rejection before end-stage renal failure and in acute rejection. V beta s 1 to 20 were quantitated by PCR in PBMC and biopsies of rejecting renal allografts. The V beta pattern in PBMC demonstrated a polyclonal distribution. However, the intragraft V beta repertoire was restricted to 1 to 3 dominant V betas and highly individual in 9 of 12 patients. Number and type of the HLA mismatch and the time interval between transplantation and biopsy did not correlate to the V beta distribution. The individual response is attributed to genetic predisposition factors of the recipient. Therefore, the restriction of the V beta repertoire indicates allo-MHC dependent immune processes not only in acute, but also in ongoing chronic rejection. Tailor-made antibodies against dominant V betas might offer specific individual immunosuppression in treating both acute and ongoing chronic rejection.
同种异体主要组织相容性复合体（MHC）特异性抗原识别可能不仅参与急性排斥反应，还参与慢性排斥反应。T细胞受体识别同种异体MHC的克隆型特异性位于可变（V）α和β链中。受限的T细胞受体库可能为慢性排斥反应提供免疫学基础。本研究的新特点是在终末期肾衰竭前的进行性慢性排斥反应和急性排斥反应中评估Vβ库。通过PCR对移植肾发生排斥反应的外周血单个核细胞（PBMC）和活检组织中的Vβ1至20进行定量分析。PBMC中的Vβ模式显示为多克隆分布。然而，移植物内的Vβ库在12例患者中的9例中局限于1至3种优势Vβ且具有高度个体性。HLA错配的数量和类型以及移植与活检之间的时间间隔与Vβ分布无关。个体反应归因于受者的遗传易感性因素。因此，Vβ库的受限表明同种异体MHC依赖性免疫过程不仅存在于急性排斥反应中，也存在于进行性慢性排斥反应中。针对优势Vβ的定制抗体可能在治疗急性和进行性慢性排斥反应中提供特异性的个体免疫抑制。
