Analysis of immunological reconstitution after allogeneic bone marrow transplantation

虽然同种异体骨髓移植（allogeneic bone marrow transplantation, alloo - bmt）是治疗恶性疾病的重要治疗手段，但机会性感染和移植物抗宿主病（graft- anti -host disease， GVHD）必须得到很好的控制，移植物中包含的T细胞也参与其中。在这项研究中，我们从T细胞相关抗原表达和T细胞激活途径的角度研究了同种异体骨髓移植后T细胞重构。CD2、CD3和CD8的表达分别在移植后1个月、3个月和6个月恢复正常。但CD4表达恢复受损超过1年，导致CD4/CD8比值长期处于低水平。在T细胞激活途径中，对糖皮质激素敏感但对环孢素耐药的CD28途径在3个月内恢复，提示该途径在急性GVHD中参与T细胞激活的重要作用。CD29 （VLA β链）表达在严重GVHD中显著升高，提示黏附分子在GVHD的发生发展中起重要作用。澄清同种异体骨髓移植后T细胞的发育和功能障碍将为GVHD的治疗方法提供理论依据。

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.