Deferiprone modulates in vitro responses by peripheral blood T cells from control and relapsing-remitting multiple sclerosis subjects.
Deferiprone modulates in vitro responses by peripheral blood T cells from control and relapsing-remitting multiple sclerosis subjects.
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去铁酮调节来自对照和复发缓解型多发性硬化症受试者的外周血 T 细胞的体外反应。
DOI：
10.1016/j.intimp.2011.07.007
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发表时间：
2011
影响因子：
5.6
通讯作者：
LeVine,StevenM
中科院分区：
文献类型：
--
作者：
Sweeney,MatthewE;Slusser,JoyceG;Lynch,SharonG;Benedict,StephenH;Garcia,SharonL;Rues,Laura;LeVine,StevenM
T 细胞是复发缓解型多发性硬化症 (RRMS) 中自身免疫炎症的重要介质。先前的研究发现，去铁酮（一种铁螯合剂）可抑制多发性硬化症小鼠模型的疾病活动，并且抑制 T 细胞增殖被认为是一种假定机制。本研究的目的是检查去铁酮对抑制对照和 RRMS 受试者 T 细胞体外反应的影响。外周血 T 细胞与抗 CD3+抗 CD28 共刺激，并在有或没有白细胞介素 2 (IL-2) 的情况下培养。来自对照和RRMS受试者的CD4+T细胞增殖，无论有或没有IL-2培养，对75μM去铁酮的反应均减少，尽管来自RRMS受试者的CD4+T细胞增殖减少的程度小于对照受试者。来自对照受试者的增殖 CD8+ T 细胞（无论有或没有 IL-2 培养）对 75μM 去铁酮的反应也有所减少，并且这种减少在来自与 IL-2 培养的 RRMS 的增殖 CD8+ T 细胞中可见。来自对照受试者的 CD4+CD25+ 和 CD8+CD25+ 细胞，在有或没有 IL-2 的情况下培养，在 75μM 去铁酮中下降，但下降幅度小于 CD4+ 和 CD8+ 增殖反应。 RRMS 受试者的 CD4+CD25+ 和 CD8+CD25+ 细胞比对照受试者表现出更大的变异性，但用 IL-2 培养的 CD4+CD25+ 细胞和不含 IL-2 培养的 CD8+CD25+ 细胞在 75μM 去铁酮中显着下降。 CD4+FoxP3+和CD4+CD25+FoxP3+细胞趋于保持恒定或增加。总之，去铁酮在血清药理学峰值浓度范围内的剂量会诱导增殖反应下降。
T cells are important mediators of autoimmune inflammation in relapsing–remitting multiple sclerosis (RRMS). Previous studies found that deferiprone, an iron chelator, suppressed disease activity in a mouse model of multiple sclerosis, and inhibition of T cell proliferation was implicated as a putative mechanism. The objective of the present study was to examine the effects of deferiprone on suppressing in vitro responses of T cells from control and RRMS subjects. Peripheral blood T cells were co-stimulated with anti-CD3+anti-CD28 and cultured with or without interleukin 2 (IL-2). Proliferating CD4+ T cells from control and RRMS subjects, cultured with or without IL-2, decreased in response to 75μM deferiprone, although the extent of decreased proliferation of CD4+ T cells from RRMS subjects was less than for control subjects. Proliferating CD8+ T cells from control subjects, cultured with or without IL-2, also decreased in response to 75μM deferiprone, and this decrease was seen in proliferating CD8+ T cells from RRMS cultured with IL-2. CD4+CD25+ and CD8+CD25+ cells from control subjects, cultured with or without IL-2, declined in 75μM deferiprone, but the decrease was smaller than for the CD4+ and CD8+ proliferative responses. CD4+CD25+ and CD8+CD25+ cells from RRMS subjects showed more variability than for control subjects, but CD4+CD25+ cultured with IL-2 and CD8+CD25+ cells cultured without IL-2 significantly declined in 75μM deferiprone. CD4+FoxP3+ and CD4+CD25+FoxP3+ cells tended to remain constant or increase. In summary, deferiprone induced declines in proliferative responses at a dosage that is within peak serum pharmacological concentrations.