趋化因子及其受体介导的T细胞向靶器官定向迁移是GVHD发生的关键环节，靶向抑制趋化因子受体（CR）的功能或表达可预防GVHD但对整体免疫功能无重大影响。尽管与GVHD发生相关的CR众多，单独敲除CCR5基因或用Maraviroc（MVC）抑制CCR5功能仍能有效抑制GVHD发生，其机制尚未阐明。应用CCR5基因敲除鼠或MVC抑制CCR5与配体结合，通过体内外对照研究证明靶向抑制CCR5预防GVHD的可能机制：①效应T细胞向CCR5配体表达水平较高的GVHD靶器官迁移减少；②CCR5与其他CR间具有交叉效应，抑制CCR5的同时也抑制了其它CR的表达；③使效应T细胞分泌更少的炎性细胞因子从而降低炎症反应，减轻GVHD发生；④改变了受者CD4+T细胞的分化能力，增加Treg的产生，从而诱导对同种异体的免疫耐受；⑤改变了受者体内Th细胞功能，使Th1/Th2/Th17平衡向抗炎的Th2极倾斜。

Chemotaxis of T cells to GVHD target organs directed by chemokines and their cognate receptors play a key role in the pathogenesis of GVHD. Targeting chemokine receptors may be an important modality in the prophylaxis of acute GVHD without affecting the whole body immunity. Although many chemokine receptors are related to the onset and progression of GVHD, only suppression of CCR5 by gene knocking out or by targeting CCR5 to inhibit its function by maraviroc could effectively prevent acute GVHD. The mechanisms underlying this preventive effect by targeting CCR5 have not been investigated. In this study, we will probe the possible mechanisms for prophylaxis of acute GVHD by targeting CCR5 using CCR5-gene knocking out mouse model to inhibit the expression and CCR5 antagonist maraviroc (MVC) to block CCR5 to bind its ligands, and through in vitro and in vivo studies to prove the hypothesis which may be as follows.⒈By targeting CCR5, less T lymphocyte trafficking to GVHD target organs or tissues where the cognate ligands for CCR5 are higher expressed.⒉ There exist a cross-talk on expression between CCR5 and other chemokine receptors. When CCR5 expression is inhibited or its function suppressed，other chemokine receptors will be disregulated which lead to inhibit T lymphocyte trafficking to GVHD target organs.⒊ Targeting CCR5 affects T lymphocyte function which result in production of less chemokines and cytokines and reduction of T lymphocyte infiltration to GVHD target organs.⒋ Targeting CCR5 may change the differentiation ability of CD4+ cells, which may lead to production of more CD4+CD25+ Foxp3+Treg cells and induction of immunotolerance to alloantigens. ⒌ Targeting CCR5 may change the function of Th cells which causes imbalance of Th1/Th2/Th17 and skew to Th2 anti-inflammation direction.