Wu F, Oka Y, Tsuboi A, Elisseeva O A, Ogata K, Nakajima H, Fujiki F, Masuda T, Murakami M, Yoshihara S, Ikegame K, Hosen N, Kawakami M, Nakagawa M, Kubota T, Soma T, Yamagami T, Tsukaguchi M, Ogawa H, Oji Y, Hamaoka T, Kawase I, Sugiyama H
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Leukemia. 2005 Feb;19(2):268-74. doi: 10.1038/sj.leu.2403539.
The Wilms' tumor gene WT1 is highly expressed in leukemias and myelodysplastic syndrome (MDS), and WT1 expression levels increase along with the disease progression in chronic myeloid leukemia and MDS. We previously reported that IgM and IgG WT1 antibodies were detected with significantly higher detection rate and antibody titers in leukemias and MDS compared to those in healthy volunteers. In this study, whether IgG humoral immune responses against WT1 protein were Th1- or Th2-type were determined by measurement of four subclasses of IgG WT1 antibody, IgG1, IgG2, IgG3, and IgG4. In leukemias and MDS, Th1-type WT1 antibodies such as IgG1, IgG2, and IgG3 were significantly increased in both detection rate and antibody titers compared to those in healthy volunteers, whereas Th2-type WT1 antibody such as IgG4 did not increase. These results showed that Th1-biased humoral immune responses against WT1 protein were generated in leukemias and MDS. These results should allow us to consider that Th1-biased cellular immune responses against WT1 protein, which was essentially needed for cancer immunotherapy targeting WT1, should be elicited in patients with hematopoietic malignancies.
威尔姆斯瘤基因WT1在白血病和骨髓增生异常综合征（MDS）中高表达，并且在慢性髓性白血病和MDS中，WT1表达水平随疾病进展而升高。我们之前报道过，与健康志愿者相比，白血病和MDS患者中IgM和IgG WT1抗体的检测率和抗体滴度显著更高。在本研究中，通过检测IgG WT1抗体的四个亚类IgG1、IgG2、IgG3和IgG4，确定针对WT1蛋白的IgG体液免疫反应是Th1型还是Th2型。在白血病和MDS中，与健康志愿者相比，Th1型WT1抗体如IgG1、IgG2和IgG3的检测率和抗体滴度均显著升高，而Th2型WT1抗体如IgG4则未升高。这些结果表明，白血病和MDS中产生了针对WT1蛋白的以Th1为主的体液免疫反应。这些结果应使我们能够认为，针对WT1蛋白的以Th1为主的细胞免疫反应（这是针对WT1的癌症免疫治疗所必需的）应在造血系统恶性肿瘤患者中引发。
