T cell receptor alpha/beta expressing double-negative (CD4-/CD8-) and CD4+ T helper cells in humans augment the production of pathogenic anti-DNA autoantibodies associated with lupus nephritis.
T cell receptor alpha/beta expressing double-negative (CD4-/CD8-) and CD4+ T helper cells in humans augment the production of pathogenic anti-DNA autoantibodies associated with lupus nephritis.
复制标题
DOI：
10.4049/jimmunol.143.1.103
复制
发表时间：
1989-07
影响因子：
4.4
通讯作者：
S. Shivakumar;G. Tsokos;S. Datta
中科院分区：
文献类型：
--
作者：
S. Shivakumar;G. Tsokos;S. Datta
一般认为，人Th细胞表达表面糖蛋白CD 4和TCR的α/β链异源二聚体，而细胞毒性/抑制细胞通常是CD 8+和α/β TCR+。在外周中发现的另一小组T细胞是CD 4-/CD 8-（双阴性）并表达γ/δ TCR;这些细胞可以表现出MHC限制性或非限制性细胞毒性，但没有辅助功能。在这里，我们描述了一个不寻常的Th人群中存在的外周血的人，CD 4-/CD 8-和α/β TCR+。这些双阴性Th在自身免疫性疾病SLE患者中显著扩增，并且沿着CD 4 + Th，它们诱导产生致病性的多种抗DNA自身抗体，其为IgG类和阳离子电荷。由Th诱导的阳离子抗DNA抗体在谱型中明显受限，表明B细胞的寡克隆群体致力于在活动性狼疮中产生致病性自身抗体。IL-2依赖性T细胞系也来源于活动性狼疮肾炎患者，但这些T细胞系中的大多数缺乏致病性自身抗体诱导能力。狼疮患者的42个T细胞系中只有4个能诱导产生阳离子IgG类抗DNA自身抗体。致病性自身抗体诱导的Th细胞系的表型与Th亚群相似：CD 4+，α/β TCR+或CD 4-/CD 8-，α/β TCR+。这些研究表明，人类狼疮中致病性自身抗体的产生是由与导致天然自身抗体过度产生的广义、非特异性多克隆B细胞过度活跃不同的机制介导的。
It is generally accepted that human Th cells express the surface glycoproteins CD4 and alpha/beta-chain heterodimer of the TCR whereas cytotoxic/suppressor cells are usually CD8+ and alpha/beta TCR+. Another minor set of T cells found in the periphery are CD4-/CD8- (double negative) and express the gamma/delta TCR; these cells can manifest MHC-restricted or nonrestricted cytotoxicity but no helper function. Herein we describe the existence of an unusual Th population in the peripheral blood of humans that are CD4-/CD8- and alpha/beta TCR+. These double-negative Th were markedly expanded in patients with the autoimmune disease SLE and along with CD4+ Th, they induced production of the pathogenic variety of anti-DNA autoantibodies that are IgG in class and cationic in charge. The cationic anti-DNA antibodies induced by the Th were markedly restricted in spectrotype indicating that an oligoclonal population of B cells were committed to produce the pathogenic autoantibodies in active lupus. IL-2-dependent T cell lines were also derived from the patients with active lupus nephritis but the majority of those T cell lines lacked pathogenic autoantibody-inducing capability. Only 4 out of 42 T cell lines from a lupus patient could induce the production of cationic IgG class anti-DNA autoantibodies. The phenotypes of the pathogenic autoantibody-inducing Th lines were similar to the Th subsets: CD4+, alpha/beta TCR+ or CD4-/CD8-, alpha/beta TCR+. These studies suggest that production of pathogenic autoantibodies in human lupus is mediated by mechanisms that are distinct from the generalized, nonspecific polyclonal B cell hyperactivity that leads to excessive production of natural autoantibodies.