Regulation of hematopoiesis in vitro by alloreactive natural killer cell clones.
Regulation of hematopoiesis in vitro by alloreactive natural killer cell clones.
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DOI：
10.1084/jem.177.4.1117
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发表时间：
1993-04-01
期刊：
影响因子：
--
通讯作者：
Trinchieri G
中科院分区：
文献类型：
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作者：
Bellone G;Valiante NM;Viale O;Ciccone E;Moretta L;Trinchieri G
自然杀伤（NK）细胞裂解自体和同种异体靶细胞，即使在靶细胞上不存在主要组织相容性复合物（MHC）I类抗原的情况下。然而，最近，已经产生了人同种异体NK细胞克隆，其识别至少五种不同的特异性，所述特异性由与MHC相关的基因遗传和控制。因为这些同种异体反应性NK细胞在体外的遗传特异性似乎类似于体内NK细胞介导的鼠杂交抗性，即，在受辐射的F1代动物中亲代骨髓的排斥反应中，我们测试了人类同种异体反应性NK克隆识别同种异体造血祖细胞的能力。来自两个特异性1同种异体反应性NK克隆ES 9和ES 10的NK细胞显著且通常完全抑制来自特异性1敏感供体的纯化外周血造血祖细胞的集落形成，但对特异性1抗性供体的细胞没有显著影响。活化的多克隆NK细胞在抑制集落形成方面的效率低于NK克隆，并且对来自特异性1敏感和耐药供体的细胞具有相似的作用。同种异体反应性NK克隆在暴露于来自特异性1敏感但不耐药供体的植物血凝素母细胞时产生对体外造血具有抑制作用的细胞因子，如干扰素γ（IFN-γ）和肿瘤坏死因子α（TNF-α）。然而，同种异体反应性NK细胞抑制集落形成的机制与直接细胞毒性作用比与抑制性细胞因子的产生更一致，因为完全阻断多克隆NK细胞抑制作用的抗体（抗IFN-γ、α-TNF-α和α-光毒素）对同种异体反应性克隆的抑制作用仅具有最小的作用。此外，同种异体反应性克隆直接溶细胞的51铬释放试验对富集制剂的外周血祖细胞从特异性1敏感的捐助者。这些数据表明，同种异体反应性NK细胞可能是人类对应的细胞介导的小鼠杂交耐药，这些细胞可能发挥重要的临床作用，在排斥反应或移植物抗白血病反应后异基因骨髓移植。
Natural killer (NK) cells lyse autologous and allogeneic target cells even in the absence of major histocompatibility complex (MHC) class I antigens on the target cells. Recently, however, human allospecific NK cell clones have been generated that recognize at least five distinct specificities inherited recessively and controlled by genes linked to the MHC. Because the genetic specificity of these alloreactive NK cells in vitro appears analogous to that of in vivo NK cell-mediated murine hybrid resistance, i.e., the rejection of parental bone marrow in irradiated F1 animals, we tested the ability of human alloreactive NK clones to recognize allogeneic hematopoietic progenitor cells. NK cells from two specificity 1 alloreactive NK clones, ES9 and ES10, significantly and often completely suppressed colony formation by purified peripheral blood hematopoietic progenitor cells from specificity 1-susceptible donors, but had no significant effect on the cells of specificity 1-resistant donors. Activated polyclonal NK cells were less efficient than the NK clones in inhibiting colony formation and had a similar effect on cells from both specificity 1-susceptible and -resistant donors. The alloreactive NK clones produced cytokines with a suppressive effect on in vitro hematopoiesis, such as interferon gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha), when exposed to phytohemagglutinin blasts from specificity 1-susceptible, but not -resistant donors. However, the mechanism by which alloreactive NK cells inhibit colony formation is more consistent with a direct cytotoxic effect than with the production of inhibitory cytokines because antibodies (anti-IFN-gamma, alpha-TNF-alpha, and -lymphotoxin) that completely blocked the inhibition by polyclonal NK cells had only a minimal effect on the inhibition by the alloreactive clones. Moreover, the alloreactive clones were directly cytolytic in a 51Cr release assay against enriched preparations of peripheral blood progenitor cells from specificity 1-susceptible donors. These data indicate that the alloreactive NK cells are likely the human counterpart of the cells mediating murine hybrid resistance and that these cells might play clinically important roles in rejection or in graft-versus-leukemia reactions after allogeneic bone marrow transplantation.