加快异基因骨髓移植（allo-BMT）后T细胞的重建，能够降低感染和肿瘤复发的几率。我们的前期研究结果表明，allo-BMT合并胸腺移植（TT）可显著增加外周CD4+ T细胞数目；在此基础上使用去CD4+ T细胞供体淋巴细胞输注[ CD4(-)-DLI ]，能够更有效地抑制肿瘤的生长。我们推测allo-BMT合并TT与CD4 (-)-DLI后，能够促进T细胞数目和功能的重建，具有更强的移植物抗肿瘤（GVT）效应。为此，本项目拟在移植后，通过：①检测外周扩增和经胸腺再生的T细胞，评价T细胞数目的重建；②检测脾脏T细胞的细胞因子反应、丝裂原反应、TCR的多样性，了解T细胞功能的重建；③检测载瘤小鼠脾脏的髓源抑制性细胞，T细胞的细胞因子分泌，肿瘤组织内供体T细胞的浸润、肿瘤细胞的凋亡，阐明其GVT效应的机制。探索一种加快allo-BMT后T细胞重建的新方法，为临床应用提供基础资料。

Strategies to enhance T cell reconstitution after allogeneic bone marrow transplantation (allo-BMT) could decrease infectious complications and malignant relapse. Results of our previous research show that thymus transplantation (TT) is able to significantly improve the percentage and number of CD4+ (but not CD8+) T cells after allo-BMT. When CD4+ T cell-depleted donor lymphocyte infusion [ CD4(-)-DLI ] is added to the allo-BMT plus TT setting, more powerful suppression of tumor growth is observed. Therefore, we hypothesize that the combination of TT and CD4(-)-DLI could enhance the reconstitution of T cell number and function and induce strong graft-versus-tumor (GVT) effects. In this subject, T cell reconstitution and the mechanism of GVT effects will be analyzed by examining the following parameters after transplantation: (1) peripheral expansion and thymus-dependent renewal of T cells; (2) cytokine response, mitogen response and TCR-Vβ families of splenic T cells; (3) myeloid-derived suppressor cells in the spleen, cytokine secretion of splenic T cells, infiltrated T cells and apoptotic tumor cells in the tumor on the tumor bearing model. We will explore a novel strategy, which has potential to be translated into clinical studies, for enhancing the T cell reconstitution after allo-BMT.