Regulation of immunities induce by GVHD, HVGD with cytokine abnormalities

细胞因子异常的 GVHD、HVGD 诱导的免疫调节

• 批准号: 06670499
• 负责人: HIRANO Takao
• 金额: $ 1.34万
• 依托单位: Juntendo University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670499/
• 关键词: GVHD; HVGD; IL-4; IgE; IgE allotype

It is well known that GVHD and HVGD are severe complications after transplantation tharapy for immunotherapies, we recently established a murine model of BMT-GVHD that was induced by the injection of parental bone marrow cells plus spleen cells as a source of T cells into irradiated F1 recipients.We found that increased serum IgE and IgG1 levels were correlated with BMT-GVHD such as liver disease and splenomegaly. The allotype of increased IgE levels in BMT-GVHD was IgE^a of donor origin, not IgE^b of host origin. We also found that in the thymus of murine BMT-GVHD, the CD4^+ CD8^+ double positive (DP) T cells were decreased, but the CD4^+ CD8^- or CD4^- CD8^+ single positive (SP) T cells were increased. When the recipients were treated with anti-IL-4 antibody (11B11), the increase of IgE and IgG1 was markedly reduced and liver disease and splenomegaly were also prevented. Moreover, abnormal T cell differentiation and maturation were suppressed. These observations suggest that IL-4 plays an important role in immunoregulation or pathogenesis of allogeneic effects and 11B11 prevents immunodysfunction including T cell differentiaiton in the thymus or the spleen and autoimmune symptoms in murine BMT-GVHD.

移植物抗宿主病（GVHD）和HVGD是移植术后的严重并发症，近年来，我们建立了一种小鼠骨髓移植物抗宿主病（BMT-GVHD）模型，用骨髓细胞和脾细胞作为T细胞来源，对F1受者进行照射，发现血清IgE和IgG_1水平升高与BMT-GVHD（如肝脏疾病和脾肿大）有关。BMT-GVHD中IgE水平升高的同种异型是供体来源的IgE^a，而不是宿主来源的IgE^B。在BMT-GVHD小鼠胸腺中，CD 4 ^+ CD 8 ^+双阳性（DP）T细胞减少，而CD 4 ^+ CD 8 ^-或CD 4 ^-CD 8 ^+单阳性（SP）T细胞增加。当接受抗IL-4抗体（11B 11）治疗时，IgE和IgG 1的增加明显减少，肝脏疾病和脾肿大也得到了预防。此外，异常的T细胞分化和成熟被抑制。这些观察结果表明，IL-4在同种异体效应的免疫调节或发病机制中起重要作用，11 B11预防免疫功能障碍，包括胸腺或脾脏中的T细胞分化和鼠BMT-GVHD中的自身免疫症状。

项目成果

Ushiyama, C.: "Anti-IL-4 antibody preveents a Graft-versus-Host diseases (GVHD) in mice after bone marrow transplantation (BMT) : IgE allotype is an important marker of GVHD." J.Immunol. 154. 2687-2696 (1995)

Ushiyama, C.：“抗 IL-4 抗体可预防骨髓移植 (BMT) 后小鼠的移植物抗宿主病 (GVHD)：IgE 同种异型是 GVHD 的重要标志物。”

USui M.: "Construction of a monoclonal antibody to Igh-7a." Immunogenetics. 37. 301-304 (1993)

USui M.：“Igh-7a 单克隆抗体的构建。”

Ushiyama,C: "Anti-IL-4 antibody prevents a Graft-versus-Host diseaes (GVHD) in mice after bone marrow transplantation (BMT) : IgE allotype is an important marker of GVHD." J. Immunol.154. 2687-2696 (1995)

Ushiyama,C：“抗 IL-4 抗体可预防骨髓移植 (BMT) 后小鼠的移植物抗宿主病 (GVHD)：IgE 同种异型是 GVHD 的重要标志物。”

C.Ushiyama et al.: "Anti-IL-4 antibody prevents a Graft-versus-Host Desease(GVHD)in mice after bone marrow transplntation (BMT):IgE allotype is an important marker of GVHD." J.Immunol.(in press). (1995)

C.Ushiyama 等人：“抗 IL-4 抗体可预防骨髓移植 (BMT) 后小鼠的移植物抗宿主病 (GVHD)：IgE 同种异型是 GVHD 的重要标志物。”

M.Yamada et al.: "Construction of a monoclonal antibody against Igh-7b." Immunogenetics.40. 296-299 (1994)

M.Yamada 等人：“抗 Igh-7b 的单克隆抗体的构建。”