Cabanillas J A, Cambronero R, Pacheco-Castro A, García-Rodríguez M C, Martín-Fernández J M, Fontán G, Regueiro J R
Deparment of Immunology, School of Medicine, Complutense University, Madrid, Spain.
Clin Exp Immunol. 2002 Feb;127(2):366-73. doi: 10.1046/j.1365-2249.2002.01716.x.
Common variable immunodeficiency (CVID) is a very frequent but heterogeneous syndrome of antibody formation. The primary defect remains unknown, but many reports describe peripheral blood T lymphocyte dysfunctions in a substantial proportion of CVID patients, which may impair T--B cell collaboration. In order to investigate whether such putative defects were intrinsic to T cells or, rather, secondary to quantitative differences in T cell subset distribution, or to other described disorders, we have used Herpesvirus saimiri (HVS) for the targeted transformation of CVID CD4+ and CD8+ T cells and subsequent functional evaluation by flow cytometry of their capacity to generate cell surface (CD154, CD69) or soluble (IL-2, TNF-alpha, IFN-gamma) help after CD3 engagement. Unexpectedly, the results showed that 40 different CVID blood samples exposed to HVS gave rise with a significantly increased frequency to transformed CD4+ T cell lines, compared to 40 age-matched controls (27% versus 3%, P < or = 0.00002) suggesting the existence of a CVID-specific signalling difference which affects CD4+ cell transformation efficiency. The functional analysis of 10 CD4+ and 15 CD8+ pure transformed T cell lines from CVID patients did not reveal any statistically significant difference as compared to controls. However, half of the CD4+ transformed cell lines showed CD154 (but not CD69) induction (mean value of 46.8%) under the lower limit of the normal controls (mean value of 82.4%, P < or = 0.0001). Exactly the same five cell lines showed, in addition, a significantly low induction of IL-2 (P < or = 0.04), but not of TNF-alpha or IFN-gamma. None of these differences were observed in the remaining CD4+ cell lines or in any of the transformed CD8+ cell lines. We conclude that certain CVID patients show selective and intrinsic impairments for the generation of cell surface and soluble help by CD4+ T cells, which may be relevant for B lymphocyte function. The transformed T cell lines will be useful to establish the biochemical mechanisms responsible for the described impairments.
普通变异型免疫缺陷（CVID）是一种非常常见但具有异质性的抗体形成综合征。其原发性缺陷尚不清楚，但许多报告描述了相当一部分CVID患者外周血T淋巴细胞功能障碍，这可能会损害T - B细胞协作。为了研究这种假定的缺陷是T细胞固有的，还是继发于T细胞亚群分布的数量差异或其他所描述的疾病，我们使用赛米利疱疹病毒（HVS）对CVID CD4 +和CD8 + T细胞进行靶向转化，并随后通过流式细胞术对其在CD3激活后产生细胞表面（CD154、CD69）或可溶性（IL - 2、TNF -α、IFN -γ）辅助分子的能力进行功能评估。出乎意料的是，结果显示，与40名年龄匹配的对照相比，40份暴露于HVS的不同CVID血样产生转化CD4 + T细胞系的频率显著增加（27%对3%，P≤0.00002），这表明存在影响CD4 +细胞转化效率的CVID特异性信号差异。对来自CVID患者的10个CD4 +和15个CD8 +纯转化T细胞系的功能分析显示，与对照相比没有任何统计学上的显著差异。然而，一半的CD4 +转化细胞系在正常对照下限（平均值82.4%）以下显示出CD154（但不是CD69）诱导（平均值46.8%，P≤0.0001）。此外，恰好相同的5个细胞系显示出IL - 2诱导显著降低（P≤0.04），但TNF -α或IFN -γ没有。在其余的CD4 +细胞系或任何转化的CD8 +细胞系中均未观察到这些差异。我们得出结论，某些CVID患者在CD4 + T细胞产生细胞表面和可溶性辅助分子方面表现出选择性和固有的损害，这可能与B淋巴细胞功能有关。转化的T细胞系将有助于确定导致所描述损害的生化机制。
