T-suppressor cells sensitive to cyclophosphamide and to its in vitro active derivative 4-hydroperoxycyclophosphamide control the mitogenic response of murine splenic B cells to dextran sulfate. A direct proof for different sensitivities of lymphocyte subsets to cyclophosphamide
T-suppressor cells sensitive to cyclophosphamide and to its in vitro active derivative 4-hydroperoxycyclophosphamide control the mitogenic response of murine splenic B cells to dextran sulfate. A direct proof for different sensitivities of lymphocyte subsets to cyclophosphamide
复制标题
对环磷酰胺及其体外活性衍生物 4-氢过氧环磷酰胺敏感的 T 抑制细胞控制小鼠脾 B 细胞对硫酸葡聚糖的有丝分裂反应。
DOI：
--
复制
发表时间：
1979
影响因子：
15.3
通讯作者：
Rg Reiman
中科院分区：
文献类型：
--
作者：
Tibor Diamantstein;Evelyne Willinger;Jc;Rg Reiman
通过[(3)H]胸腺嘧啶摄取测定，小鼠脾脏细胞在7天前注射单剂量的环磷酰胺（Cy） （125 mg x kg(-1)），对葡聚糖（DS）的反应增强，对脂多糖（LPS）的反应减弱，对豆豆蛋白a的反应正常。在脾脏细胞中加入同基因胸腺细胞抑制了细胞对DS的增强反应，并略微增强了它们对LPS的反应。体外用4-羟基过氧环磷酰胺（4HP-Cy）预处理胸腺细胞（Cy的体外活性衍生物）可消除胸腺细胞对DS反应的影响，但对LPS反应没有影响。体外小剂量4HP-Cy （0.1 ~ 1.0 μg. ml(-1)）预处理脾脏细胞可增强细胞对DS的应答能力，但不影响甚至降低细胞对LPS的应答能力。使用缺乏T细胞或缺乏功能T细胞的脾脏细胞，无法检测到4HP-Cy处理对DS反应的增强。4HP-Cy剂量超过3 μ ml（-1）可降低或消除脾细胞对LPS的应答能力以及对DS的应答能力。结果表明(a)与lps反应性b淋巴细胞亚群相比，ds反应性b淋巴细胞亚群的增殖能力受到Cy-和4HP-Cy敏感T细胞亚群的负性控制；(b)这些T抑制细胞对Cy和4HP-Cy（对各自的活性烷基化代谢物）比b淋巴细胞和具有其他免疫功能的T细胞更敏感。
As measured by [(3)H]thymidine uptake, spleen cells of mice injected 7 d previously with a single dose of cyclophosphamide (Cy) (125 mg x kg (-1)) gave an enhanced response to dextran sulfate (DS), a diminished response to lipopolysaccharide (LPS), and a normal response to concanavalin A. Addition of syngeneic thymocytes to spleen cells inhibited the enhanced response of the cells to DS and slightly enhanced their response to LPS. Pretreatment of thymocytes by 4-hydroxyperoxycyclophosphamide (4HP-Cy) in vitro (an in vitro active derivative of Cy) abrogated the effect of thymocytes on the DS response but not on the LPS response. Pretreatment of spleen cells by small doses of 4HP-Cy (0.1-1.0 μg. ml(-1)) in vitro enhanced the capacity of the cells to respond to DS but either did not affect, or even diminished their capacity to respond to LPS. The enhancement of the DS response by 4HP-Cy treatment could not be detected using spleen cells depleted of T cells or lacking functioning T cells. 4HP-Cy doses more than 3 μg ml(-1) diminished or abolished the capacity of the spleen cells to respond to LPS as well as their capacity to respond to DS. The results show (a) that in contrast to the LPS-reactive B-lymphocyte subset, the proliferative capacity of DS-reactive subset is negatively controlled by a Cy- and 4HP-Cy-sensitive T-cell subset and (b) that these T- suppressor cells are more sensitive to Cy and 4HP-Cy (to their respective active alkylating metabolites) than B lymphocytes and T cells carrying other immunological functions.