IMMUNOSUPPRESSION IN THALASSEMIA

我们一直在调查输血铁与 重型地中海贫血患者的超负荷与免疫功能我们有 研究表明，B细胞活化在本病中存在，并伴有 NK功能降低。B细胞活化的增加和减少 在NK功能方面与输血有关。我们还表明， 体外应用铁络合剂可逆转NK细胞活性下降的趋势。 最近研究表明，NK细胞在很大程度上调节B细胞的功能 动物和人体实验系统的范围。我们建议调查 地中海贫血患者NK细胞与B细胞相互作用的研究 首先，如果存在缺乏监管的情况，如果存在，是否可以扭转 用螯合预先孵育地中海贫血单核细胞的NK富集组分 探员们。我们还希望区分免疫功能的变化 由输血本身和铁超载引起的免疫调查 接受输血但没有铁的患者的功能 超负荷(肾脏透析)和调查有铁的患者 超负荷，但输血很少(中间地中海贫血， 特发性血色沉着症)。这些研究应该能让我们深入了解 NK细胞在调节B细胞功能中的作用及应提供的证据 关于螯合治疗是否会导致整体改善或 只是对免疫防御机制的重新调整。

We have been investigating the relationship between transfusional iron overload and immune function in patients with -thalassemia major. We have shown that B-cell activation exists in this disease concomitant with decreased NK function. Both the increase in B-cell activation and decrease in NK function are transfusion-related. We have also shown that the decreased NK activity can be reversed by iron-chelating agents in vitro. NK cells have recently been shown to regulate B-cell function in a wide range of animal and human experimental systems. We propose to investigate the interaction between NK cells and B-cells in thalassemia to determine first if a lack of regulation exists and if so whether it can be reversed by preincubation of NK-enriched fractions of thalassemia MNC with chelating agents. We also hope to distinguish between changes in immune function resulting from transfusion per se and iron overload by investigating immune function in patients who receive blood transfusions but do not have iron overload (kidney dialysis) and by investigating patients who have iron overload but receive few if any transfusions (thalassemia intermedia, idiopathic hemochromatosis). These studies should provide insight into the role of NK cells in regulating B-cell function and should provide evidence as to whether chelation therapy will result in an overall improvement or merely a readjustment of immunological defense mechanisms.