IMMUNOSUPPRESSION IN THALASSEMIA

我们一直在研究输血铁和 重型β地中海贫血患者免疫功能的变化 我们有 表明B细胞活化存在于这种疾病中， NK功能下降。 B细胞活化的增加和减少 NK功能与输血有关。 我们还表明， 降低的NK活性可以通过铁螯合剂在体外逆转。 NK细胞最近已被证明在广泛的免疫调节中调节B细胞功能。 一系列动物和人类实验系统。 我们建议调查 地中海贫血中NK细胞和B细胞之间的相互作用，以确定 首先，是否存在监管缺失，如果存在，是否可以扭转 通过将地中海贫血MNC的富含NK的部分与螯合剂预孵育， 剂. 我们也希望区分免疫功能的变化 通过研究免疫功能， 接受输血但没有铁的患者的功能 超负荷（肾透析）和调查患者谁有铁 超负荷但接受很少的输血（中间型地中海贫血， 特发性血色病）。 这些研究应该提供深入了解 NK细胞在调节B细胞功能中的作用，并应提供证据 关于螯合治疗是否会导致整体改善， 仅仅是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.