Barrett A John, Le Blanc Katarina
Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Best Pract Res Clin Haematol. 2008 Jun;21(2):165-76. doi: 10.1016/j.beha.2008.02.004.
Graft-versus-host disease (GVHD) is the immune response of donor T lymphocytes responding to the recipient's alloantigens. The cellular and cytokine mechanisms driving GVHD are now well defined and have led to several prophylactic approaches. Selective allodepletion techniques promise to prevent GVHD without causing immune deficiency provoked by global T-cell depletion. Targeted dosing of other (non-T-cells) cells in the graft - such as CD34+ progenitors, regulatory T cells, natural killer cells and mesenchymal stromal cells - can also lead to transplants designed to retain immune capability without causing GVHD. Immunosuppressive drugs such as methotrexate, cyclosporine and anti-lymphocyte antibodies are the mainstay in the prevention of GVHD and can be used in conjunction with engineered grafts to eliminate GVHD. In future it is anticipated that further refinements in targeting the elimination or suppression of the GVHD reacting T cells should be selective enough to preserve the important graft-versus-leukemia effect which contributes to the cure of malignant diseases by allogeneic stem-cell transplantation.
移植物抗宿主病（GVHD）是供体T淋巴细胞对受体同种异体抗原产生的免疫反应。驱动GVHD的细胞和细胞因子机制现已明确，这也带来了多种预防方法。选择性去除同种异体技术有望预防GVHD，同时不会因全面T细胞去除而引发免疫缺陷。对移植物中的其他（非T细胞）细胞进行靶向给药，如CD34+祖细胞、调节性T细胞、自然杀伤细胞和间充质基质细胞，也能实现旨在保留免疫能力且不引发GVHD的移植。免疫抑制药物，如甲氨蝶呤、环孢素和抗淋巴细胞抗体，是预防GVHD的主要手段，可与经过改造的移植物联合使用以消除GVHD。未来预计，在靶向消除或抑制引发GVHD的T细胞方面的进一步改进应具有足够的选择性，以保留重要的移植物抗白血病效应，该效应有助于通过异基因干细胞移植治愈恶性疾病。
