Analysis of immunological reconstitution after allogeneic bone marrow transplantation

异体骨髓移植后免疫重建分析

• 批准号: 06670778
• 负责人: SUGITA Kanji
• 金额: $ 1.28万
• 依托单位: Yamanashi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06670778/
• 关键词: allogeneic bone marrow transplantation; T cell dysfunction; CD28; CD29; CD29; 免疫学的再構築; T細胞

Although allogeneic bone marrow transplantation (allo-BMT) is an important therapeutic approach for the treatment of malignant diseases, opportunistic infection and graft-versus-host disease (GVHD), in which T cells included in grafts are involved, must be well controled. In this study, we examined T cell reconstitution after allo-BMT in terms of T cell-related antigen expression and T cell activation pathways. The expression of CD2, CD3, and CD8 bacame normal at 1 month, 3 month, and 6 month, respectively, post allo-BMT.However, recovery of CD4 expression was impaired more than 1 year, thus resulting in long-term low CD4/CD8 ratio. Among T cell activation pathways, the CD28 pathway, which is sensitive to glucocorticoid but resistant to cyclosporin, recovered within 3 months, suggesting an important role of this pathway in T cell activation involved in acute GVHD.The CD29 (VLA beta-chain) expression was significantly increased in cases with severe GVHD,which suggests an crucial role of adhesion molecules in development of GVHD.Clarification of T cell development and dysfunction post allo-BMT will provide a theoretical basis with therapeutic approach to GVHD.

异基因骨髓移植（allo-BMT）是治疗恶性肿瘤的重要手段，但移植物中T细胞参与的机会性感染和移植物抗宿主病（GVHD）仍需严格控制。在这项研究中，我们研究了T细胞相关抗原表达和T细胞活化途径的异基因骨髓移植后的T细胞重建。异基因骨髓移植后1、3、6个月CD_2、CD_3、CD_8表达恢复正常，但CD_4表达恢复受阻，1年后CD_4/CD_8比值长期偏低。在T细胞活化途径中，对糖皮质激素敏感但对环孢菌素耐药的CD 28途径在3个月内恢复，表明该途径在参与急性GVHD的T细胞活化中起重要作用。（VLA β-链）表达在严重GVHD的病例中显著增加，阐明allo-BMT后T细胞的发育和功能障碍将为GVHD的治疗提供理论依据。

项目成果

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Sugita.K.：“在 T 细胞耗尽的同种异体骨髓移植后，通过 CD3 途径，极晚活化抗原介导的 T 细胞增殖受到长期损害。”

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Kanji Sugita：“使用抗磷酸化酪氨酸抗体诊断 Ph^1 阳性急性淋巴细胞白血病”医学史 170. 966-968 (1994)。

Kameoka J: "Differential CD26 mediated activation of the CD3 and CD2 pathways after CD6-depleted allogeneic bone marrow transplantation." Blood. 85. 1132-1137 (1995)

Kameoka J：“CD6 耗尽的同种异体骨髓移植后，差异 CD26 介导的 CD3 和 CD2 通路激活。”

Inukai.T: "Analysis of cytoplasmic and surface antigen in childhood T-cell acute lymphoblastic leukemias:clinical relevance of cytoplasmic TCR β chain." Brit.J.Haematol.87. 273-281 (1994)

Inukai.T：“儿童 T 细胞急性淋巴细胞白血病的细胞质和表面抗原分析：细胞质 TCR β 链的临床相关性。Brit.J.Haematol.87（1994 年）”

Jun Kameoka: "Differential CD26 mediated activation of the CD3 and CD2 pathways after CD6-depleted allogeneic bone marrow transplantation." Blood. 85. 1132-1137 (1995)

Jun Kameoka：“CD6 耗尽的同种异体骨髓移植后，差异 CD26 介导 CD3 和 CD2 通路的激活。”