Effect of intermediate‐purity factor VIII (FVIII) concentrate on lymphocyte proliferation and apoptosis: transforming growth factor‐β is a significant immunomodulatory component of FVIII
Effect of intermediate‐purity factor VIII (FVIII) concentrate on lymphocyte proliferation and apoptosis: transforming growth factor‐β is a significant immunomodulatory component of FVIII
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中等纯度因子 VIII (FVIII) 浓缩物对淋巴细胞增殖和凋亡的影响：转化生长因子-β 是 FVIII 的重要免疫调节成分
DOI：
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发表时间：
2001
影响因子：
6.5
通讯作者：
P. Han
中科院分区：
文献类型：
--
作者：
G. Hodge;P. Han
因子浓缩物已被证明具有多种体外免疫调节作用。血浆衍生因子VIII （pdFVIII）的存在已被证明可以减少淋巴细胞对有丝分裂原的增殖反应。最近，我们已经证明转化生长因子β (TGF - β)作为一种免疫调节成分存在于血浆衍生的FVIII浓缩物中。然而，TGF - β中和抗体的加入并没有消除pdFVIII对单核细胞细胞因子产生的抑制作用，这表明pdFVIII中存在其他尚未确定的免疫调节剂。为了进一步表征pdFVIII的免疫调节作用，我们用全血和纯化的T细胞研究了pdFVIII浓缩液对丝裂原刺激的T细胞增殖和凋亡的体外影响。pdFVIII的存在增加了植物血凝素（PHA）刺激的CD4和CD8 T细胞亚群的凋亡，这是通过膜联蛋白V结合和DNA断裂来确定的。T细胞亚群显示pdFVIII剂量依赖性抑制进入S期和G1停滞。加入中和抗TGF - β可以减少这些变化。为了确定这些发现的生理学相关性，我们对5例接受FVIII预防治疗的患者的血液样本进行了类似的体外研究，结果显示，通过Annexin V染色，T细胞亚群的凋亡明显增加。据报道，TGF - β是T细胞增殖的有效抑制剂，在G1期阻止细胞周期并导致细胞凋亡。总之，这些发现表明TGF‐β是pdFVIII浓缩物的重要免疫调节成分。
Factor concentrates have been shown to have a variety of immunomodulatory effects in vitro. The presence of plasma‐derived factor VIII (pdFVIII) has been shown to diminish lymphocyte proliferative response to mitogens. Recently, we have shown the presence of transforming growth factor‐β (TGF‐β) as an immunomodulatory component present in plasma‐derived FVIII concentrate. However, the addition of neutralizing antibody to TGF‐β did not abrogate the inhibitory effect of pdFVIII on monocyte cytokine production, suggesting the presence of other, as yet undetermined, immunomodulatory agent/s in pdFVIII. To further characterize the immunomodulatory effects of pdFVIII, the in vitro effect of pdFVIII concentrate on proliferation and apoptosis of mitogen‐stimulated T cells was studied using whole blood and purified T cells. The presence of pdFVIII increased the apoptosis of phytohaemagglutinn (PHA) ‐stimulated CD4 and CD8 T‐cell subsets as determined by Annexin V binding and DNA fragmentation. T‐cell subsets showed a pdFVIII dose‐dependent inhibition of entry into S‐phase and G1 arrest. Addition of neutralizing anti‐TGF‐β reduced some of these changes. To determine the physiological relevance of these findings, blood samples from five patients receiving FVIII prophylaxis were similarly studied ex vivo and showed significantly increased apoptosis of T‐cell subsets as determined by Annexin V staining. TGF‐β has been reported to be a potent inhibitor of T‐cell proliferation, arresting the cell cycle in G1 phase and causing apoptosis. Together, these findings suggest that TGF‐β is a significant immunomodulatory component of pdFVIII concentrates.
用因子浓缩物治疗的血友病受试者出现迟发性皮肤超敏反应。
DOI：
10.1016/0002-9343(86)90545-0
发表时间：
1986
期刊：
The American journal of medicine
影响因子：
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作者：
Brettler,DB;Forsberg,AD;Brewster,F;Sullivan,JL;Levine,PH
通讯作者：
Levine,PH