DIFFERENTIAL INHIBITION OF PRIMED ALLOREACTIVE CTLs IN VITRO BY CLINICALLY USED CONCENTRATIONS OF CYCLOSPORINE AND FK506
DIFFERENTIAL INHIBITION OF PRIMED ALLOREACTIVE CTLs IN VITRO BY CLINICALLY USED CONCENTRATIONS OF CYCLOSPORINE AND FK506
复制标题
环孢菌素和 FK506 临床使用浓度对体外引发的同种反应性 CTL 的差异抑制
DOI：
10.1097/00007890-199307000-00035
复制
发表时间：
1993
期刊：
影响因子：
6.2
通讯作者：
F. Claas
中科院分区：
文献类型：
--
作者：
D. Roelen;F. P. van Bree;U. Schanz;J. V. van Rood;F. Claas
先前在等待肾移植的高致敏患者中的研究表明，同种抗体的形成与同种抗原特异性细胞毒性T细胞前体频率之间缺乏相关性。针对HLA I类抗原的CTLp的频率，患者已形成针对其的抗体（不可接受的错配，NAM），与针对HLA抗原的CTLp的频率相似，不存在针对其的抗体（可接受的错配，AM）。在最近的研究中，我们测试了导致抗体形成的免疫触发是否可能导致不同的细胞毒性T细胞群体。在不存在或存在针对CD8的抗体的情况下进行的有限稀释测定表明，针对NAM的CTL与针对AM的CTL相比，抗CD8的抑制显著降低。这些“致敏的”CTL也可以根据它们对环孢霉素的抗性而与更“幼稚的”CTL区分开。与CsA相比，治疗浓度的FK506能够抑制“初始”和“致敏”CTL。目前正在研究这些数据的临床相关性。
Previous studies in highly sensitized patients waiting for a renal transplant showed a lack of correlation between the formation of alloantibodies and the alloantigen-specific cytotoxic T cell precursor frequency. The frequencies of CTLp against HLA class I antigens, toward which patients had formed antibodies (not acceptable mismatches, NAM), were similar to those against HLA antigens, toward which no antibodies were present (acceptable mismatches, AM). In more recent studies we tested whether the immunological triggering leading to antibody formation might have resulted in a different population of cytotoxic T cells. Limiting dilution assays performed in the absence or presence of antibodies against CD8 showed that CTL directed against NAM were significantly less inhibited by anti-CD8 compared with those directed against AM. Those “primed” CTL could also be distinguished from the more “naive” CTL on the basis of their resistance to cyclosporine. In contrast to CsA, therapeutic concentrations of FK506 were able to inhibit both “naive” and “primed” CTLs. The clinical relevance of these data is currently being investigated.