Analysis of gene defects related to NK cell deficiency : Establishment of the disorder as a new immunodeficiency

本研究旨在分析自然杀伤（NK）细胞缺乏症的临床特点及基因缺陷。家族性NK细胞缺陷（Komiyama， A.，儿科）(1)随着年龄的增长，循环中的rdT细胞数量逐渐增加，对感染的超易感性似乎有所改善。(2)患者有CD56+细胞，均为CD3+CD56+细胞，而非CD3-CD56+细胞。这些结果表明，这种疾病是由于缺乏循环NK细胞。(3)然后，通过体外培养骨髓细胞来检测NK细胞前体的增殖能力。在多种细胞因子或饲养层+ IL-2存在的情况下，我们无法在培养系统中培养CD3-CD56+细胞。需要进一步的研究来阐明这些缺陷。(4)穿孔素mRNA在细胞毒性T细胞中表达正常。Chediak-Higashi综合征(1)NK细胞对K562细胞活性缺陷，而对Jurkat细胞活性几乎正常。后一种活性不受肿瘤坏死因子-a的影响。(2) perin介导的细胞毒性受损，但其mRNA在NK细胞中表达正常。(3) Fas mRNA表达正常，Fas/Fas配体介导细胞凋亡的细胞毒性正常。其他疾病，如噬血细胞综合征，系统性红斑狼疮，NK细胞异常与切尔诺贝利事故有关。这些疾病中的NK细胞缺陷在本研究中也进行了类似的分析。

The present studies were conducted to analyze the clinical chatacteristics and gene defects of natural killer (NK) cell deficiencies.1. Familial NK cell deficieny (Komiyama, A., Pediatr., 85 : 323,1990)(1) The hypersusceptibility to infections appears to be improved with age, with a gradual increase in the number of circulating rdT cells.(2) The patients have CD56+ cells, all of which are CD3+CD56+ cells but not CD3-CD56+ cells. These results indicate that this disorder is due to the absence of circulating NK cells.(3) Then, next studies were performed to examine the proliferative capacity of NK cell precursors by culturing the bone marrow cells in vitro. We failed to culture CD3-CD56+ cells in the presence of a combination of many cytokines or feeder layrs + IL-2 in the culture system. Further studies are necessary to elucidate the defects.(4) The expression of perforin mRNA was normal in the cytotoxic T cells.2. Chediak-Higashi syndrome(1) NK cell activity was defective against K562 cells but almost normal against Jurkat cells. The latter activity was not exerted by tumor necrosis factor-a.(2) The perfor in-mediated cytotoxicity was impaired, but its mRNA was normally expressedin the NK cells.(3) The Fas mRNA expression was normal, and Fas/Fas ligand-mediated cytotoxicity via apoptosis was normal.3.Other disorders such as hemophagocytic syndrome, systemic lupus erythematosus, and NK cell abnormality related to the Chernobyl accident.The NK cell deficiencies in these disordeers were similarly analyzed in the present studies.