Zadeh H H, Kreutzer D L
Department of Periodontology, University of Southern California, School of Dentistry, Los Angeles 90089-0641, USA.
Oral Microbiol Immunol. 1996 Apr;11(2):88-95. doi: 10.1111/j.1399-302x.1996.tb00341.x.
Immunomodulation by periodontopathic bacteria has been implicated in the pathogenesis of inflammatory periodontal diseases. A novel class of microbial-derived T cell mitogens, referred to as superantigens, has recently been described. Superantigens are unique in that they induce a tremendous activation and expansion of specific subsets of T cells in an antigen-independent manner, thereby causing immune dysfunction. Subsets of superantigen-expanded T cells can be identified with reagents that discriminate among different families of the variable domains of the T cell antigen receptor beta-chain (V beta). Since superantigens expand one or a few of these T cell antigen receptor V beta families, T cell subsets that have been expanded by superantigens have restricted expression of one or a few V beta families. In the present study, we investigated the presence of putative superantigen-stimulated T cells in periodontitis sites, utilizing a panel monoclonal antibodies to T cell antigen receptor V beta families. Leukocytes were isolated from gingival tissues obtained from 8 periodontitis and 4 non-periodontitis patients by collagenase digestion. Three-color flow cytometric analysis of these gingival cells demonstrated that in most periodontitis patients examined, patterns of V beta expression among T cells are characteristic of superantigen stimulation, i.e., there is an elevation in the proportion of one or a few V beta families. Specifically, these analyses revealed that T cell subsets expressing V beta 5a and V beta 5b, V beta 6, V beta 8 and V beta 12 were each elevated greater than 2 standard deviations in at least one periodontitis patient compared with the mean of the non-periodontitis subjects. In some periodontitis patients, a less marked elevation of T cells that express V beta 3, V beta 5a, V beta 5b, V beta 6, V beta 8, V beta 12, and V beta 13 was noted (greater than 1 standard deviation higher than the mean of the V beta families in non-periodontics subjects). Interestingly, V beta 8+ T cells were elevated to some degree in all periodontitis patients examined. In contrast, T cells expressing V beta 2, V beta 17 and V beta 19 were not significantly different in any of the subjects studied. In most periodontitis but not non-periodontitis patients, up to 50% of all gingival T cells expressed one or a few T cell antigen receptor V beta families, suggesting that superantigens constitute a major pathway of T cell activation and expansion. Hence, our data support the hypothesis that a large proportion of T cells in periodontitis sites have been stimulated and expanded by superantigens, presumably produced by periodontitis-associated bacteria.
牙周病原菌的免疫调节作用与炎症性牙周疾病的发病机制有关。最近描述了一类新型的微生物来源的T细胞有丝分裂原，称为超抗原。超抗原的独特之处在于它们以抗原非依赖的方式诱导特定T细胞亚群的大量激活和扩增，从而导致免疫功能紊乱。可以用区分T细胞抗原受体β链（Vβ）可变区不同家族的试剂来鉴定超抗原扩增的T细胞亚群。由于超抗原扩增这些T细胞抗原受体Vβ家族中的一个或几个，因此被超抗原扩增的T细胞亚群具有一个或几个Vβ家族的受限表达。在本研究中，我们利用一组针对T细胞抗原受体Vβ家族的单克隆抗体，研究了牙周炎部位假定的超抗原刺激T细胞的存在情况。通过胶原酶消化从8名牙周炎患者和4名非牙周炎患者的牙龈组织中分离白细胞。对这些牙龈细胞进行三色流式细胞术分析表明，在大多数接受检查的牙周炎患者中，T细胞中Vβ表达模式具有超抗原刺激的特征，即一个或几个Vβ家族的比例升高。具体而言，这些分析显示，与非牙周炎受试者的平均值相比，至少有一名牙周炎患者中表达Vβ5a和Vβ5b、Vβ6、Vβ8和Vβ12的T细胞亚群各自升高超过2个标准差。在一些牙周炎患者中，观察到表达Vβ3、Vβ5a、Vβ5b、Vβ6、Vβ8、Vβ12和Vβ13的T细胞有较不明显的升高（比非牙周炎受试者Vβ家族平均值高超过1个标准差）。有趣的是，在所有接受检查的牙周炎患者中，Vβ8 + T细胞均有一定程度的升高。相比之下，表达Vβ2、Vβ17和Vβ19的T细胞在任何研究对象中均无显著差异。在大多数牙周炎患者而非非牙周炎患者中，所有牙龈T细胞中高达50%表达一个或几个T细胞抗原受体Vβ家族，这表明超抗原构成了T细胞激活和扩增的主要途径。因此，我们的数据支持这样的假设，即牙周炎部位的大部分T细胞已被超抗原刺激和扩增，推测这些超抗原是由牙周炎相关细菌产生的。
