Activation of human B lymphocytes. XII. Differential effects of in vitro cyclophosphamide on human lymphocyte subpopulations involved in B-cell activation.
Activation of human B lymphocytes. XII. Differential effects of in vitro cyclophosphamide on human lymphocyte subpopulations involved in B-cell activation.
复制标题
人类 B 淋巴细胞的激活。
作者：
H. Stevenson;A. Fauci
本文研究了环磷酰胺（CY）对正常人外周血淋巴细胞亚群的不同影响，这些亚群参与美洲商陆丝裂原诱导的空斑形成细胞（PFC）对绵羊红细胞的反应。发现该系统中的空斑形成B细胞在宽浓度范围内对CY敏感，包括对总细胞活力具有最小影响的浓度。动力学实验表明，CY发挥其对PFC反应的抑制作用，只有当加入非常早的文化。因此，看来，在体外CY必须发挥其抑制多克隆B细胞活化的早期阶段的影响。当富含T细胞（TCE）的群体与高浓度CY孵育过夜，然后在共培养物中添加回新鲜自体B细胞时，观察到PFC应答的显著增强，表明选择性抑制或消除TCE淋巴细胞制剂中发现的调节抑制细胞群体。辅助T细胞对CY的抑制作用具有相对抗性。因此，人B细胞似乎对CY最敏感，其次是T细胞部分中的抑制细胞群体，具有辅助T细胞的相对抗性。这些观察结果有直接的相关性，在了解CY对正常人淋巴细胞亚群的选择性作用的机制，可能适用于人类疾病状态。
The differential effects of in vitro cyclophosphamide (CY) on subpopulations of normal human peripheral blood lymphocytes involved in the pokeweed mitogen-induced plaque-forming cell (PFC) response against sheep red blood cells were examined. It was found that the plaque-forming B cells in this system are sensitive to CY over a wide concentration range including concentrations which have a minimal effect on overall cell viability. Kinetic experiments revealed that CY exerts its inhibitory effect on the PFC response only if added very early in culture. Thus, it appears that in vitro CY must exert its inhibitory influence on an early phase of polyclonal B-cell activation. When T-cell enriched (TCE) populations were incubated overnight with high concentration CY and then added back in co-culture to fresh autologous B cells, significant enhancement of PFC responses was observed suggesting a selective inhibition or elimination of a regulatory suppressor cell population found in TCE lymphocyte preparations. Helper T cells are relatively resistant to the inhibitory actions of CY. Thus, human B cells appear to be most sensitive to CY, followed in sensitivity by the suppressor cell populations in the T-cell fraction with relative resistance of the helper T cells. These observations have direct relevance in understanding the mechanisms of selective action of CY on normal human lymphocyte subpopulations with possible application to disease states in man.