FREQUENCY OF HUMAN ALLOANTIGEN‐REACTIVE T LYMPHOCYTES
FREQUENCY OF HUMAN ALLOANTIGEN‐REACTIVE T LYMPHOCYTES
复制标题
人类同种抗原反应性 T 淋巴细胞的频率
DOI：
--
复制
发表时间：
1988
期刊：
影响因子：
--
通讯作者：
R. Ferguson
中科院分区：
文献类型：
--
作者：
C. Orosz;P. Adams;R. Ferguson
我们使用限制稀释分析来研究来自人外周血的同种抗原反应性T淋巴细胞的行为。在这些研究中，我们发现环孢素在限制稀释微培养中的存在显著损害了异体抗原反应性细胞溶解T细胞活性的后续发展。因此，CsA通过限制稀释分析降低了CTL前体频率的估计。CsA以剂量依赖性的方式降低CTL频率估计，在人外周血中容易达到的CsA浓度（100 - 1000 ng/ml）能够将CTL频率估计降低90%至100%。进一步的研究表明：(1)来源于新鲜外周血或原代混合淋巴细胞培养的人CTL在限制稀释的微培养中对环孢素的抑制作用敏感，表明CsA影响同种异体抗原引物CTL和CTL前体；(2) CsA损害至少在限制稀释微培养孵育的前四天内发生的一个或多个免疫事件；(3) CsA介导的抑制作用可通过环孢素分离CTL消除；(4)在限制稀释的微培养中，CsA阻断CTL的产生，但不阻断细胞增殖；(5) CsA介导的抑制不会被超优浓度的IL - 2、高浓度的γ - IFN或补充MLC上清中存在的多种淋巴因子逆转。这些数据表明，CsA可能对人CTL前体的分化有直接的抑制作用，而不依赖于辅助性T细胞功能障碍。
We have used limiting dilution analysis to study the behavior of alloantigen‐reactive cytolytic T lymphocytes derived from human peripheral blood. During these studies, we found that the presence of cyclosporine in limiting dilution microcultures significantly impairs the subsequent development of alloantigen‐reactive cytolytic T cell activity. As a result, CsA reduces the estimate of CTL precursor frequency by limiting dilution analysis. CTL frequency estimates are reduced by CsA in a dose‐dependent manner, and concentrations of CsA that are readily achieved in human peripheral blood (100‐1000 ng/ml) are capable of reducing estimates of CTL frequency by 90% to 100%. Further studies revealed that (1) human CTL derived either from fresh peripheral blood or from primary mixed lymphocyte cultures are sensitive to the suppressive effects of cyclosporine in limiting dilution microcultures, indicating that CsA influences both alloantigen‐primed CTL and CTL precursors; (2) CsA impairs an immunologic event or events, that occurs for at least the first four days of limiting dilution microculture incubation; (3) CsA‐mediated suppression is eliminated by separation of CTL from cyclosporine; (4) CsA blocks development of CTL generation, but not cell proliferation in limiting dilution microcultures; and (5) the CsA‐mediated suppression is not reversed by supraoptimal concentrations of IL‐2, high concentrations of gamma‐IFN, or supplementation with the multiple lymphokines present in MLC supernatants. These data suggest that CsA may have a direct inhibitory influence on the differentiation of human CTL precursors that is independent of helper T cell dysfunction.