研究证据表明，次级淋巴器官（SLO）是诱导免疫耐受发生的重要场所，这种现象可发生于肿瘤和异体器官移植诱导的免疫耐受，其MDSC及其相关细胞可能起重要作用。该研究拟确定SLO中微环境FRC为诱导免疫耐受的中心环节，不仅直接抑制T细胞增殖和活化，也可促使MDSC及相关细胞生成发挥对T细胞活化的抑制作用。应用已建立的GVHD模型和阻断T细胞趋化使T细胞滞留于SLO而预防GVHD模型证明T细胞在SLO中的活化程度低于GVHD靶器官中T细胞活化程度，靶向阻断趋化因子受体使T细胞滞留于SLO可进一步抑制T细胞活化，这种免疫抑制作用与MDSC生成有关。本研究拟通过对比分析SLO和GVHD靶器官免疫细胞和免疫相关分子的差异，初步阐明SLO诱导免疫耐受机制。该研究的意义在于确定在allo-HSCT条件下SLO是免疫耐受诱导器官，FRC及其诱导扩增的MDSC及其相应细胞是诱导免疫耐受的中心环节。

More and more evidences demonstrated that secondary lymphatic organs (SLOs) are important sites for immune tolerance induction. This phenomenon not only take place in tumor-induced but also in allograft-induced immune tolerance.MDSC and its related antigen-presenting cells may be important in this process. In this study, we will probe the microenvironment in SLOs, especially fibroblastic reticular cells (FRC),play a central role in immune tolerance. It not only directly inhibit proliferation and activation of conventional T cells, but it may promote the expension of MDSC and its related cells in SLOs. Also, FRC might promote the expression of checkpoint molecular PD-L1/2 and other immune inhibitory moleculars on antigen-presenting cells which may induce T cell tolerance. We will try to conform that T cells in SLOs is less activated than that in GVHD organ such as liver through a murine GVHD model. Our previous studies showed that blockade of chemokine receptors could lead to retention of donor-derived T cells to SLOs and attenuate murine acute GVHD. We try to use established murine GVHD model and T cell SLO retention model by blockage of chemokine receptors to illuminate the cellular and molecular mechanisms underlying SLO-induced immune tolerance through comparative study of immune cells and immune-related molecular in SLOs and GVHD-targeted organs. Though these series studies, we might confirm that SLOs are immune tolerance-induced organs under the condition of allo-HSCT，FRC as well as MDSC and its related cells expended from myeloid progenitor cells in graft may play a central role in inducing immune tolerance.