Analysis of immunological reconstitution after allogeneic bone marrow transplantation

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)必须得到很好的控制。在这项研究中，我们从T细胞相关抗原的表达和T细胞激活途径的角度研究了allo-BMT后T细胞的重建。异基因骨髓移植后1个月、3个月、6个月CD2、CD3、CD8细胞的表达均正常，但CD4的恢复受阻1年以上，导致长期的低CD4/CD8比值。在T细胞活化途径中，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的T细胞活化中起重要作用。CD29(VLAβ链)在重度GVHD患者中表达显著增加，提示黏附分子在GVHD的发生发展中起关键作用。阐明异基因骨髓移植后T细胞的发育和功能障碍将为GVHD的治疗提供理论依据。

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.