Department of Neurology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD, USA.
Cell Immunol. 2013 Jul-Aug;284(1-2):68-74. doi: 10.1016/j.cellimm.2013.06.011. Epub 2013 Jul 2.
Double-negative T (DNT) cells are αβTCR(+)CD3(+)CD4(-)CD8(-)NK1.1(-) cells that constitute a small but significant proportion of the αβTCR(+) T cells. Their developmental pathway and pathological significance remain unclear. In the present study, we utilized chronic in vitro stimulation of CD4(+) T cells to mimic immune hyper-activation of autoimmune lymphoproliferative syndrome and systemic lupus erythematosus, conditions characterized by DNT cells accumulation. After approximately 4-5 rounds of stimulation, the CD3(+)CD4(-) population became apparent. These cells did not express CD8, NK1.1, γδTCR, or B220, exhibited a highly proliferative effector phenotype, and were dependent on T cell receptor (TCR) stimulation for survival. Moreover, CD3(+)CD4(-) cells expressed MHC class II-restricted αβTCR, indicative of their origin from a CD4(+) T cell population. The results presented herein illustrate a novel method of DNT cell generation in vitro and suggest that immune hyper-activation could also be implicated in the genesis of the disease-associated DNT cells in vivo.
双阴性 T（DNT）细胞是一种 αβT 细胞受体（TCR）阳性、CD3 阳性、CD4 阴性、CD8 阴性、NK1.1 阴性的细胞，它们构成了 αβTCR 阳性 T 细胞的一小部分，但具有重要意义。它们的发育途径和病理意义尚不清楚。在本研究中，我们利用 CD4+T 细胞的慢性体外刺激来模拟自身免疫性淋巴组织增生综合征和系统性红斑狼疮等自身免疫性疾病的免疫过度激活，这些疾病的特征是 DNT 细胞的积累。经过大约 4-5 轮刺激后，CD3+CD4-群体变得明显。这些细胞不表达 CD8、NK1.1、γδTCR 或 B220，表现出高度增殖的效应器表型，并且依赖于 T 细胞受体（TCR）刺激来存活。此外，CD3+CD4-细胞表达 MHC 类 II 限制的 αβTCR，表明它们起源于 CD4+T 细胞群体。本文介绍了一种体外 DNT 细胞生成的新方法，并提示免疫过度激活也可能与体内疾病相关的 DNT 细胞的发生有关。
