June Carl H, Blazar Bruce R
The Abramson Family Cancer Research Institute, The Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Semin Immunol. 2006 Apr;18(2):78-88. doi: 10.1016/j.smim.2006.01.006. Epub 2006 Feb 2.
A central goal immunologists has been to develop targeted therapies that will induce or maintain immunologic tolerance in the absence of potentially harmful immunosuppression. The ability to isolate and expand regulatory T-cell populations with immune suppressive activity will enable new forms of adoptive immunotherapy that may achieve this long held dream. Assuming that certain technical challenges regarding the manufacturing of regulatory T cells can be overcome, a wide variety of clinical applications can be envisioned using adoptively transferred CD4(+)CD25(+) regulatory T cells. It is likely that suppressor T cells will first be tested for their ability to prevent or treat graft-versus-host disease (GVHD) following allogeneic bone marrow or stem cell transplantation. A related approach will be clinical studies to induce allogeneic or xenogeneic tolerance using regulatory T cells in solid organ transplantation. A more technically challenging approach will be the use of regulatory T-cell therapy for autoimmune disorders. Finally on the horizon are approaches that will use genetically engineered lymphocytes to replace regulatory T cells in the immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome, and potentially to create more potent regulatory T (Treg) cells with enhanced suppressive activity.
免疫学家的一个核心目标是开发靶向疗法，在不使用潜在有害的免疫抑制的情况下诱导或维持免疫耐受。分离并扩增具有免疫抑制活性的调节性T细胞群体的能力，将促成新形式的过继性免疫疗法，有望实现这一长久以来的梦想。假设在调节性T细胞制造方面的某些技术挑战能够被克服，那么使用过继性转移的CD4(+)CD25(+)调节性T细胞可设想出各种各样的临床应用。抑制性T细胞很可能首先会在异基因骨髓或干细胞移植后，接受预防或治疗移植物抗宿主病（GVHD）能力的测试。一种相关的方法将是在实体器官移植中使用调节性T细胞诱导同种异体或异种耐受的临床研究。一种技术上更具挑战性的方法将是使用调节性T细胞疗法治疗自身免疫性疾病。最后即将出现的方法是，利用基因工程淋巴细胞替代免疫失调、多内分泌腺病、肠病、X连锁（IPEX）综合征中的调节性T细胞，并有可能创造出具有更强抑制活性的更有效的调节性T（Treg）细胞。
