Bleesing Jack J H, Brown Margaret R, Novicio Cynthia, Guarraia David, Dale Janet K, Straus Stephen E, Fleisher Thomas A
Department of Laboratory Medicine, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Clin Immunol. 2002 Jul;104(1):21-30. doi: 10.1006/clim.2002.5225.
The discovery of an unusual T-cell subset characterized by the expression of the alpha/beta T-cell receptor without expression of either CD4 or CD8 [alpha/beta-double-negative T cells (alpha/beta-DNTCs)] provided critical insights in the evaluation of a "new" lymphoproliferative disorder known as autoimmune lymphoproliferative syndrome (ALPS). ALPS is a disorder of defective Fas-mediated lymphocyte apoptosis, manifested by accumulation of alpha/beta-DNTCs and other lymphocyte subsets, leading to lymphadenopathy and splenomegaly, autoimmunity, and an increased risk of lymphoma. The expanded population of alpha/beta-DNTCs from ALPS patients has a remarkable uniform phenotype that is for the most part similar to alpha/beta-DNTCs from mice with defective Fas (lpr) or Fas ligand (gld). This is in contrast to the minor alpha/beta-DNTC compartment in healthy individuals that contains multiple, immunophenotypically distinct subpopulations. Current data indicate that alpha/beta-DNTCs from ALPS patients are derived from cytotoxic CD8(+) T cells, chronically activated in vivo but anergic in vitro. Their anergic state may be related to persistent modifications of O-linked carbohydrates on cell surface molecules, such as CD43 and CD45, as well as to the increased presence of interleukin-10. Although largely consistent with a model of (linear) CD8(+) cytotoxic T-cell differentiation, the expression patterns of certain surface molecules, such as CD27 and CD28, are not consistent with this model. This may be the result of the perturbed homeostasis of lymphocytes in ALPS, thereby revealing pathways of differentiation and immunophenotypes, including phenotypes pertaining to cell surface glycosylation that are hidden from view in healthy individuals.
一种不寻常的T细胞亚群的发现为评估一种名为自身免疫性淋巴细胞增生综合征（ALPS）的“新型”淋巴增生性疾病提供了关键见解。该亚群以表达α/β T细胞受体但不表达CD4或CD8为特征 [α/β双阴性T细胞（α/β-DNTCs）]。ALPS是一种Fas介导的淋巴细胞凋亡缺陷性疾病，表现为α/β-DNTCs和其他淋巴细胞亚群的积累，导致淋巴结病和脾肿大、自身免疫以及淋巴瘤风险增加。来自ALPS患者的α/β-DNTCs扩增群体具有显著一致的表型，在很大程度上类似于来自Fas缺陷（lpr）或Fas配体缺陷（gld）小鼠的α/β-DNTCs。这与健康个体中较小的α/β-DNTC区室形成对比，后者包含多个免疫表型不同的亚群。目前的数据表明，来自ALPS患者的α/β-DNTCs源自细胞毒性CD8(+) T细胞，在体内长期活化但在体外无反应性。它们的无反应状态可能与细胞表面分子（如CD43和CD45）上O-连接碳水化合物的持续修饰以及白细胞介素-10的增加有关。尽管在很大程度上与（线性）CD8(+) 细胞毒性T细胞分化模型一致，但某些表面分子（如CD27和CD28）的表达模式与该模型不一致。这可能是ALPS中淋巴细胞稳态受到干扰的结果，从而揭示了分化途径和免疫表型，包括与细胞表面糖基化相关的表型，而这些表型在健康个体中是隐藏的。
