Abrams Kraig, Graves Scott S, Parker Maura H, Storb Rainer
Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
Department of Medicine, University of Washington, Seattle, WA.
Transplant Direct. 2020 Nov 16;6(12):e632. doi: 10.1097/TXD.0000000000001082. eCollection 2020 Dec.
Complementary, marrow donor-derived peripheral blood T-lymphocyte infusions enable consistent hematopoietic engraftment in lethally irradiated dog leukocyte antigen (DLA)-haploidentical littermate recipients, but at the cost of severe graft versus host disease (GVHD). Here, we explored whether CD94-selected and in vitro-expanded natural killer (NK) cells could be substituted for T-lymphocytes for enhancing marrow engraftment without causing severe GVHD.
Five dogs were conditioned with 700 cGy total body irradiation followed by infusion of DLA-haploidentical donor marrow and CD94-selected, in vitro-expanded NK cells. NK cells were infused at a median of 140 000 (range 78 000-317 000) cells/kg.
Four dogs rejected their marrow grafts, whereas 1 dog fully engrafted and developed GVHD. We observed an increase in peripheral blood NK cells after infusion of CD94-selected, ex vivo-expanded NK in 2 dogs. Peripheral blood lymphocyte counts peaked at day 7 or 8 posttransplant in the 4 rejecting dogs, whereas in the fully engrafted dog, lymphocyte counts remained stable at suboptimal levels.
Our study indicates NK cells can be expanded in vitro and safely infused into DLA-haploidentical recipients. Within the range of CD94-selected and expanded cells infused we concluded that they failed to both uniformly promote engraftment and avert GVHD.
补充供体来源的外周血T淋巴细胞输注可使接受致死剂量照射的犬白细胞抗原（DLA）半相合同窝受体实现稳定的造血植入，但代价是严重的移植物抗宿主病（GVHD）。在此，我们探讨了经CD94筛选并体外扩增的自然杀伤（NK）细胞是否可替代T淋巴细胞以增强骨髓植入且不引发严重GVHD。
5只犬接受700 cGy全身照射预处理，随后输注DLA半相合供体骨髓及经CD94筛选并体外扩增的NK细胞。NK细胞的输注剂量中位数为140 000（范围78 000 - 317 000）个细胞/千克。
4只犬排斥其骨髓移植，而1只犬实现完全植入并发生GVHD。我们观察到，2只犬在输注经CD94筛选并体外扩增的NK细胞后外周血NK细胞增加。4只发生排斥反应的犬外周血淋巴细胞计数在移植后第7天或第8天达到峰值，而在完全植入的犬中，淋巴细胞计数维持在次优水平且保持稳定。
我们的研究表明NK细胞可在体外扩增并安全输注至DLA半相合受体体内。在输注经CD94筛选并扩增的细胞范围内，我们得出结论，它们未能既统一促进植入又避免GVHD。
