Role of natural killer cells on engraftment of human lymphoid cells and on metastasis of human T-lymphoblastoid leukemia cells in C57BL/6J-scid mice and in C57BL/6J-scid bg mice
Role of natural killer cells on engraftment of human lymphoid cells and on metastasis of human T-lymphoblastoid leukemia cells in C57BL/6J-scid mice and in C57BL/6J-scid bg mice
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DOI：
10.1006/cimm.1996.9998
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发表时间：
1996-08-01
影响因子：
4.3
通讯作者：
Shultz, LD
中科院分区：
文献类型：
--
作者：
Christianson, SW;Greiner, DL;Shultz, LD
为研究自然杀伤细胞（NK细胞）在正常和恶性淋巴造血细胞排斥反应中的作用，将严重联合免疫缺陷（scid）突变株与C57 BL/6 J株回交。C57 BL/6 J-scid/scid小鼠表现出严重的成熟T和B细胞丢失，伴有NK 1.1（+）细胞和髓系细胞百分比增加。尽管在2月龄之前很少或没有血清免疫球蛋白可检测，但所有测试的小鼠在7.5月龄时具有循环免疫球蛋白。与C57 BL/6 J-+/+对照组相比，C57 BL/6 J-scid/scid小鼠的溶血性补体活性和NK细胞活性均显著升高。每周注射抗NK1.1抗体导致C57 BL/6 J-scid/scid小鼠中NK细胞活性在整个8周治疗期间消除。尽管人CEM-C7 T淋巴母细胞样肿瘤细胞在未操作的C57 BL/6 J-scid/scid小鼠中生长缓慢，但抗NK 1.1治疗导致生长增加，并伴有人淋巴瘤细胞转移至脑、肝和肾。与T淋巴母细胞样肿瘤细胞相反，非恶性的人外周血单核细胞在抗NK1.1治疗的C57 BL/6-scid/scid小鼠中以低水平移植。米色（bg（J））突变与C57 BL/6-scid/scid遗传原种的回交导致NK细胞活性降低，伴有粒细胞缺陷。C57 BL/6-scid/scid bg（J）/bg（J）小鼠显示人CEM-C7细胞转移至脑和其他器官，但仅支持低水平的人外周血单核细胞植入。这些结果表明，在缺乏适应性免疫系统的情况下，NK细胞对人淋巴瘤的转移具有抗性，并表明除了NK细胞功能之外，先天免疫因子介导对正常人外周血白细胞植入的抗性。(C)出版社：Academic Press，Inc.
The severe combined immunodeficiency (scid) mutation was backcrossed onto the C57BL/6J strain background in order to study the role of natural killer (NK) cells in rejection of normal and malignant human lymphohematopoietic cells. C57BL/6J-scid/scid mice showed severe loss of mature T and B cells accompanied by increased percentages of NK1.1(+) cells and myeloid cells. Although little or no serum immunoglobulin was detectable prior to 2 months of age, all mice tested had circulating immunoglobulin by 7.5 months of age. C57BL/6J-scid/scid mice had markedly elevated levels of both hemolytic complement activity and NK cell activity compared with C57BL/6J-+/+ controls. Weekly injections with anti-NK1.1 antibody resulted in elimination of NK cell activity in C57BL/6J-scid/scid mice throughout 8 weeks of treatment. Although human CEM-C7 T lymphoblastoid tumor cells grew slowly in unmanipulated C57BL/6J-scid/scid mice, anti-NK1.1 treatment resulted in increased growth accompanied by metastasis of human lymphoma cells to the brain, liver, and kidney. In contrast to T lymphoblastoid tumor cells, nonmalignant human peripheral blood mononuclear cells engrafted at low levels in anti-NK1.1-treated as well as in unmanipulated C57BL/6-scid/scid mice. Backcrossing of the beige (bg(J)) mutation onto the C57BL/6-scid/scid genetic stock caused decreased NK cell activity accompanied by granulocyte defects. C57BL/6-scid/scid bg(J)/bg(J) mice showed metastasis of human CEM-C7 cells to the brain and other organs but supported only low levels of engraftment with human peripheral blood mononuclear cells. These results demonstrate that NK cells, in the absence of an adaptive immune system, function in resistance to metastasis of human lymphomas and suggest that innate immune factors in addition to NK cell function mediate resistance to engraftment of normal human peripheral blood leukocytes. (C) 1996 Academic Press, Inc.