Nozawa Hayabusa, Kishibe Kan, Takahara Miki, Harabuchi Yasuaki
Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical College, Midorigaoka Higashi 2-1-1-1, Asahikawa, Hokkaido 078-8510, Japan.
Clin Immunol. 2005 Jul;116(1):42-53. doi: 10.1016/j.clim.2005.01.009.
Pustulosis palmaris et plantaris (PPP) is known to be a one of the tonsil-related diseases because tonsillectomy is quite effective in curing this condition. However etiological association between tonsils and PPP have not fully clarified yet. Cutaneous lymphocyte-associated antigen (CLA) is known to be a specific homing receptor that facilitates T-cell migration into skin. In this study, we investigated the expression of CLA on T-cells in tonsil, peripheral blood, and skin from patients with PPP. Two-color flow cytometric and two-color immunohistological analyses revealed that the numbers of CLA/CD3 double-positive cells in freshly isolated tonsillar mononuclear cells (TMC) and in tonsillar tissues were significantly higher in patients with PPP than in patients without PPP (P<0.01, each). In vitro stimulus with alpha-streptococcal antigens enhanced CLA expression of tonsillar T-cells and TGF-beta production of TMC in patients with PPP (P<0.01, each), but did not in patients without PPP. In peripheral blood from PPP patients, the number of the CLA/CD3 double-positive cells significantly decreased at 6 months after tonsillectomy (P<0.05). The CLA/CD3 double-positive cells and the postcapillary venule that expressed with a ligand of CLA, E-selectin, were found more frequently in the plantar skin from patients with PPP as compared to that from healthy volunteers (P<0.01, each). These data suggest that a novel immune response to alpha-streptococci may enhance CLA expression on tonsillar T-cells through TGF-beta production in patients with PPP, resulting in moving of CLA-positive tonsillar T-cells to skin and tissue damages. This may play a key role in pathogenesis of PPP.
掌跖脓疱病(PPP)被认为是与扁桃体相关的疾病之一,因为扁桃体切除术对治愈这种疾病非常有效。然而,扁桃体与PPP之间的病因学关联尚未完全阐明。皮肤淋巴细胞相关抗原(CLA)是一种促进T细胞迁移至皮肤的特异性归巢受体。在本研究中,我们调查了PPP患者扁桃体、外周血和皮肤中T细胞上CLA的表达情况。双色流式细胞术和双色免疫组织学分析显示,新鲜分离的扁桃体单个核细胞(TMC)和扁桃体组织中CLA/CD3双阳性细胞的数量在PPP患者中显著高于非PPP患者(均P<0.01)。用α-链球菌抗原进行体外刺激可增强PPP患者扁桃体T细胞的CLA表达和TMC的TGF-β产生(均P<0.01),但在非PPP患者中则无此现象。在PPP患者的外周血中,扁桃体切除术后6个月CLA/CD3双阳性细胞的数量显著减少(P<0.05)。与健康志愿者相比,PPP患者足底皮肤中CLA/CD3双阳性细胞以及表达CLA配体E-选择素的毛细血管后微静脉更为常见(均P<0.01)。这些数据表明,PPP患者对α-链球菌的一种新的免疫反应可能通过TGF-β产生增强扁桃体T细胞上的CLA表达,导致CLA阳性的扁桃体T细胞迁移至皮肤并造成组织损伤。这可能在PPP的发病机制中起关键作用。