Johnson B D, Dagher N, Stankowski W C, Hanke C A, Truitt R L
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Biol Blood Marrow Transplant. 2001;7(11):589-95. doi: 10.1053/bbmt.2001.v7.pm11760146.
Donor regulatory T cells (CD3+ alphabetaT-cell receptor [TCR]+) derived from the repopulating host thymus have been shown to be primarily responsible for suppression of GVHD following DLI therapy in murine BMT models. However, natural killer (NK) T cells also have regulatory properties, and a role for NK T cells in suppression of GVH reactivity has not been completely excluded. NK cells may also contribute to the graft-versus-leukemia (GVL) effect associated with DLI therapy. In this study, we used a murine BMT model (C57BL/6 into AKR) to study whether depletion of donor NK cells had any impact on the suppression of GVH reactivity after DLI or on the DLI-induced GVL effect against acute T-cell leukemia. Depletion of donor NK cells was accomplished in vivo by giving DLI-treated bone marrow chimeras multiple injections of anti-NK1.1 monoclonal antibody (MoAb). The chimeras treated with anti-NK1.1 MoAb had significantly fewer splenic NK1.1 cells than nontreated chimeras, and splenocytes from anti-NK1.1-treated mice were deficient in the ability to generate lymphokine-activated lytic activity. Results presented here showed that NK-cell depletion had no effect on the suppression of GVH reactivity after DLI. When DLI-treated chimeras were challenged with an acute T-cell leukemia, NK-cell depletion had no discernible effect on GVL reactivity. These preclinical data suggest that donor NK cells do not have a significant role in the suppression of GVHD after DLI or in the mediation of GVL reactivity induced by DLI.
在小鼠骨髓移植模型中，已证明源自再植宿主胸腺的供体调节性T细胞（CD3⁺αβT细胞受体[TCR]⁺）主要负责抑制供体淋巴细胞输注（DLI）治疗后的移植物抗宿主病（GVHD）。然而，自然杀伤（NK）T细胞也具有调节特性，并且尚未完全排除NK T细胞在抑制GVH反应性中的作用。NK细胞也可能有助于与DLI治疗相关的移植物抗白血病（GVL）效应。在本研究中，我们使用小鼠骨髓移植模型（C57BL/6小鼠移植到AKR小鼠）来研究供体NK细胞的耗竭是否对DLI后GVH反应性的抑制或对DLI诱导的针对急性T细胞白血病的GVL效应有任何影响。通过给接受DLI治疗的骨髓嵌合体多次注射抗NK1.1单克隆抗体（MoAb），在体内实现供体NK细胞的耗竭。用抗NK1.1 MoAb处理的嵌合体的脾脏NK1.1细胞明显少于未处理的嵌合体，并且来自抗NK1.1处理小鼠的脾细胞产生淋巴因子激活的溶解活性的能力不足。此处给出的结果表明，NK细胞耗竭对DLI后GVH反应性的抑制没有影响。当用急性T细胞白血病攻击接受DLI治疗的嵌合体时，NK细胞耗竭对GVL反应性没有明显影响。这些临床前数据表明，供体NK细胞在DLI后GVHD的抑制或DLI诱导的GVL反应性的介导中没有显著作用。
