Blazar B R, Korngold R, Vallera D A
Department of Pediatrics, University of Minnesota Hospital and Clinics, Minneapolis 55455, USA.
Immunol Rev. 1997 Jun;157:79-109. doi: 10.1111/j.1600-065x.1997.tb00976.x.
In the 1970s and 1980s, GVHD prevention approaches were limited in number. Recent advances in our understanding of the requirements for T-cell immune responses and for basic mechanism(s) involved in GVHD pathophysiology have led to exciting new strategies for GVHD prevention. This review focuses upon recent developments in GVHD prevention generated over the past 5 years. We have selected five different types of strategies to highlight including: 1) the in vivo targeting of GVHD-reactive T cells using either intact and F(ab')2 fragments of monoclonal antibodies directed against T-cell-surface determinants or immunotoxins which consist of antibodies linked to toxins, 2) a comparison of the in vivo immunosuppressive effects of FK506 and rapamycin on T-cell signaling, 3) the inhibition of T-cell activation through blockade of costimulatory or adhesogenic signals, 4) shifting the balance between acute GVHD-inducing T-helper-type 1 (Th1) T cells to anti-inflammatory T-helper-type 2 (Th2)-type T cells, and 5) the regulation of alloreactive T-cell activation by treatment with peptide analogs which affect either TCR/MHC, CD4/MHC class II, or CD8/MHC class I interactions. Collectively, these approaches are illustratrative of the progress made in extending our GVHD prevention armamentarium.
在20世纪70年代和80年代，移植物抗宿主病（GVHD）的预防方法数量有限。近年来，我们对T细胞免疫反应的需求以及GVHD病理生理学所涉及的基本机制的理解取得了进展，从而产生了令人兴奋的GVHD预防新策略。本综述聚焦于过去5年中GVHD预防方面的最新进展。我们选择了五种不同类型的策略进行重点介绍，包括：1）使用针对T细胞表面决定簇的单克隆抗体的完整片段和F(ab')2片段或由与毒素相连的抗体组成的免疫毒素在体内靶向GVHD反应性T细胞；2）比较FK506和雷帕霉素对T细胞信号传导的体内免疫抑制作用；3）通过阻断共刺激或黏附信号来抑制T细胞活化；4）将诱导急性GVHD的T辅助1型（Th1）T细胞与抗炎性T辅助2型（Th2）T细胞之间的平衡进行转变；5）用影响TCR/MHC、CD4/MHC II类或CD8/MHC I类相互作用的肽类似物处理来调节同种反应性T细胞活化。总体而言，这些方法说明了我们在扩展GVHD预防手段方面所取得的进展。
