Rodríguez-Gallego C, Corell A, Pacheco A, Timón M, Regueiro J R, Allende L M, Madroño A, Arnaiz-Villena A
Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, Spain.
J Immunol Methods. 1996 Nov 13;198(2):177-86. doi: 10.1016/s0022-1759(96)00156-1.
The characterization of T cell immunodeficiencies could in part be supported by using stable cell lines in which biochemical and molecular studies of the defect could be carried out thereby omitting frequent bleeding of patients. First attempts to obtain such cell lines included HTLV-I transformation and exogenous IL-2 administration, but both models have important disadvantages. Recently, a virus isolated from the squirrel monkey, Herpes virus saimiri (HVS), has been reported to have the ability to transform T cells. A stable IL-2-dependent HVS-transformed T cell line from a CD3 gamma deficient patient has been obtained; and this cell line displays both the phenotypic and the functional characteristics of the patient's lymphocytes. Moreover, the line down-modulates TCR/CD3 surface expression upon CD3 engagement, as do the patient's lymphocytes, showing that CD3 gamma and its phosphorylation are not necessary for TCR/CD3 internalization. In addition, the abnormal staining pattern of different anti-TCR/CD3 monoclonal antibodies is preserved in the HVS-patient line. Since HVS is capable of transforming CD3 gamma- T cells, the CD3 gamma chain does not seem to be involved in the HVS receptor process. The fact that it is not possible to obtain a CD8+ HVS line from the CD3 gamma- patient supports the existence of a functional anomaly in his scanty CD8+ peripheral lymphocytes. Thus, HVS transformation is a suitable model for T cell immunodeficiency studies and characterization. It may also be used in the future in cellular models for in vitro gene therapy trials.
利用稳定的细胞系可以部分支持对T细胞免疫缺陷的特征描述，在这些细胞系中可以对缺陷进行生化和分子研究，从而避免患者频繁出血。获得此类细胞系的最初尝试包括HTLV-I转化和外源性白细胞介素-2给药，但这两种模型都有重要缺陷。最近，据报道，从松鼠猴分离出的一种病毒——猴疱疹病毒（HVS）具有转化T细胞的能力。已从一名CD3γ缺陷患者获得了一种稳定的依赖白细胞介素-2的HVS转化T细胞系；该细胞系表现出患者淋巴细胞的表型和功能特征。此外，与患者淋巴细胞一样，该细胞系在CD3激活后会下调TCR/CD3表面表达，表明CD3γ及其磷酸化对于TCR/CD3内化并非必需。此外，不同抗TCR/CD3单克隆抗体的异常染色模式在HVS患者细胞系中得以保留。由于HVS能够转化CD3γ- T细胞，CD3γ链似乎不参与HVS受体过程。无法从CD3γ-患者获得CD8+ HVS细胞系这一事实支持了其稀少的CD8+外周淋巴细胞存在功能异常。因此，HVS转化是T细胞免疫缺陷研究和特征描述的合适模型。未来它也可能用于体外基因治疗试验的细胞模型中。
