Diluvio Laura, Vollmer Sigrid, Besgen Petra, Ellwart Joachim W, Chimenti Sergio, Prinz Joerg C
Department of Dermatology, Ludwig-Maximilians-University of Munich, Munich, Germany.
J Immunol. 2006 Jun 1;176(11):7104-11. doi: 10.4049/jimmunol.176.11.7104.
Tonsillar infection with Streptococcus pyogenes may induce several nonsuppurative autoimmune sequelae. The precise pathogenetic mechanisms behind this clinically well-established association are still unresolved. Using TCR analysis, we sought to identify a link between streptococcal tonsillitis and the T cell-mediated autoimmune response in psoriasis. Three patients with streptococcal-induced psoriasis underwent tonsillectomy. Using size spectratyping and sequencing of TCR beta-chain variable region gene (TCRBV) rearrangements, we compared the TCR usage of psoriatic skin lesions, blood, tonsils, and tonsillar T cells fractionated according to the expression of the skin address in "cutaneous lymphocyte-associated Ag" (CLA). TCRBV-size spectratype analysis of the blood lymphocytes, tonsils, and the CLA-negative tonsillar T cells revealed largely unselected T cell populations. Instead, TCRBV gene families of the psoriatic lesions and skin-homing CLA-positive tonsillar T cells displayed highly restricted spectratypes. Sequencing of TCRBV cDNA identified various clonal TCRBV rearrangements within the psoriatic lesions that indicated Ag-driven T cell expansion. Several of these clonotypes were also detected within the tonsils and, in one of the patients, within the small subset of CLA-positive tonsillar T cells, suggesting that T cells from the same T cell clones were simultaneously present within skin and tonsillar tissue. Because after tonsillectomy psoriasis cleared in all three patients our observations indicate that T cells may connect psoriatic inflammation to streptococcal angina. They suggest that the chronic streptococcal immune stimulus within the tonsils could act as a source for pathogenic T cells in poststreptococcal disorders, and they may help to explain why eliminating this source with tonsillectomy may improve streptococcal-induced sequelae.
化脓性链球菌引起的扁桃体感染可能会诱发多种非化脓性自身免疫后遗症。这种临床上已明确的关联背后的确切发病机制仍未解决。我们通过TCR分析，试图确定链球菌性扁桃体炎与银屑病中T细胞介导的自身免疫反应之间的联系。三名链球菌诱发银屑病的患者接受了扁桃体切除术。我们使用大小谱型分析和TCRβ链可变区基因（TCRBV）重排测序，比较了银屑病皮肤病变、血液、扁桃体以及根据“皮肤淋巴细胞相关抗原”（CLA）中皮肤归巢表达进行分离的扁桃体T细胞的TCR使用情况。对血液淋巴细胞、扁桃体和CLA阴性扁桃体T细胞进行的TCRBV大小谱型分析显示，T细胞群体在很大程度上未被选择。相反，银屑病病变和皮肤归巢CLA阳性扁桃体T细胞的TCRBV基因家族显示出高度受限的谱型。TCRBV cDNA测序在银屑病病变中鉴定出各种克隆性TCRBV重排，这表明抗原驱动的T细胞扩增。在扁桃体中也检测到了其中几种克隆型，并且在其中一名患者的CLA阳性扁桃体T细胞小亚群中也检测到了，这表明来自相同T细胞克隆的T细胞同时存在于皮肤和扁桃体组织中。由于在扁桃体切除术后，所有三名患者的银屑病都得到了缓解，我们的观察结果表明，T细胞可能将银屑病炎症与链球菌性扁桃体炎联系起来。它们表明扁桃体中的慢性链球菌免疫刺激可能是链球菌感染后疾病中致病性T细胞的来源，并且它们可能有助于解释为什么通过扁桃体切除术消除这个来源可能会改善链球菌诱发的后遗症。
