Yarkoni Shai, Stein Jerry, Yaniv Isaac, Askenasy Nadir
Cellect Biomed , Kfar Saba , Israel.
Bone Marrow Transplant Unit, Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel , Petah Tikva , Israel.
Front Immunol. 2014 May 19;5:215. doi: 10.3389/fimmu.2014.00215. eCollection 2014.
Prophylactic approaches to graft versus host disease (GvHD) have employed both phenotypic reduction of T cells and selective elimination of host-primed donor T cells in vitro and in vivo. An additional approach to GvHD prophylaxis by functional depletion of apoptosis-sensitive donor T cells without host-specific sensitization ex vivo showed remarkable reduction in GHD incidence and severity. We address the role and significance of antigen-specific sensitization of donor T cells and discuss the mechanisms of functional T cell purging by apoptosis for GvHD prevention. Host-specific sensitization is dispensable because migration is antigen-independent and donor T cell sensitization is mediated by multiple and redundant mechanisms of presentation of major and minor histocompatibility complex and tissue antigens by donor and host antigen-presenting cells. Our data suggest that potential murine and human GvH effectors reside within subsets of preactivated T cells susceptible to negative regulation by apoptosis prior to encounter of and sensitization to specific antigens.
移植物抗宿主病（GvHD）的预防方法包括在体外和体内对T细胞进行表型减少以及选择性清除宿主致敏的供体T细胞。另一种通过在体外对凋亡敏感的供体T细胞进行功能耗竭来预防GvHD的方法，且无需宿主特异性致敏，结果显示GHD的发生率和严重程度显著降低。我们探讨了供体T细胞抗原特异性致敏的作用和意义，并讨论了通过凋亡进行功能性T细胞清除以预防GvHD的机制。宿主特异性致敏是不必要的，因为迁移不依赖抗原，且供体T细胞致敏是由供体和宿主抗原呈递细胞呈递主要和次要组织相容性复合体及组织抗原的多种冗余机制介导的。我们的数据表明，潜在的小鼠和人类移植物抗宿主效应细胞存在于预激活T细胞亚群中，这些亚群在遇到特定抗原并致敏之前易受凋亡的负调控。
