Pawankar R U, Okuda M, Suzuki K, Okumura K, Ra C
Department of Otolaryngology, Nippon Medical School, Japan.
Am J Respir Crit Care Med. 1996 May;153(5):1655-65. doi: 10.1164/ajrccm.153.5.8630617.
T cells expressing the T-cell receptor (TCR) gamma delta home in on various epithelia and may play an important role in local immunity to foreign antigens. The nasal mucosa is a potential site for chronic inflammatory diseases, yet little is known about the characteristics of nasal mucosal gamma delta T cells. Using flow cytometry, immunohistochemistry, and RT-PCR, we elucidated the characteristics of nasal mucosal gamma delta T cells in patients with perennial allergic rhinitis (PAR), chronic infective rhinitis (CIR), and seasonal allergic rhinitis (SAR) and in normal subjects. The gamma delta T cells were significantly increased in the nasal mucosa of patients with PAR (PAR, 24.3 +/- 4.5%; CIR, 12.9+/- 2.7%, p < 0.01), unrelated to those in autologous peripheral blood (PAR, 5.6 +/- 0.8%; CIR, 9.6 +/- 2.8%), and they were preferentially distributed in the epithelial compartment (26.7 +/- 2.3%) rather than in the lamina propria (5.4 +/- 2.5%). Of the expanded population of nasal mucosal gamma delta T cells in patients with PAR, CD4+ and CD4-8- gamma delta T cells were selectively increased (p < 0.01). Although nasal intraepithelial gamma delta T cells from all groups of patients and normal subjects dominantly expressed the V gamma 1/V delta 1 genes, and a bias for V gamma 3 gene expression was noted in those of patients with PAR, a significantly larger fraction of nasal mucosal gamma delta T cells in patients with PAR expressed the V gamma 1/V delta 1 TCR (p, 0.01), whereas those of the peripheral blood expressed the V gamma 2/V delta 2 TCR. More than 60% of V gamma 1/V delta 1 TCR+ cells in patients with PAR, were CD45RO+ ("memory cells"), independent of those in their peripheral blood (p < 0.01). Furthermore, a substantial proportion of nasal mucosal gamma delta T cells in patients with PAR synthesized IL-4 and IL-5 but negligible amounts of IFN-gamma. These observations of an increase in the proportions and activation of distinct subsets of nasal mucosal gamma delta T cells and their Th2-type cytokine profile in patients with PAR, unrelated to those in autologous peripheral blood suggest an important role for the oligoclonally expanded expanded nasal mucosal gamma delta T cells in the pathogenesis of PAR.
表达γδ T细胞受体（TCR）的T细胞定位于各种上皮组织，可能在对外来抗原的局部免疫中发挥重要作用。鼻粘膜是慢性炎症性疾病的潜在发病部位，但对鼻粘膜γδ T细胞的特征了解甚少。我们运用流式细胞术、免疫组织化学和逆转录聚合酶链反应（RT-PCR），阐明了常年性变应性鼻炎（PAR）、慢性感染性鼻炎（CIR）、季节性变应性鼻炎（SAR）患者以及正常受试者鼻粘膜γδ T细胞的特征。PAR患者鼻粘膜中的γδ T细胞显著增多（PAR为24.3±4.5%；CIR为12.9±2.7%，p<0.01），与自身外周血中的γδ T细胞数量无关（PAR为5.6±0.8%；CIR为9.6±2.8%），且它们优先分布于上皮层（26.7±2.3%）而非固有层（5.4±2.5%）。在PAR患者中，鼻粘膜γδ T细胞扩增群体里，CD4⁺和CD4⁻8⁻γδ T细胞选择性增多（p<0.01）。尽管所有患者组和正常受试者的鼻上皮内γδ T细胞主要表达Vγ1/Vδ1基因，且在PAR患者中观察到Vγ3基因表达有偏向性，但PAR患者鼻粘膜γδ T细胞中表达Vγ1/Vδ1 TCR的比例显著更高（p=0.01），而外周血中的γδ T细胞表达Vγ2/Vδ2 TCR。PAR患者中超过60%的Vγ1/Vδ1 TCR⁺细胞为CD45RO⁺（“记忆细胞”），与外周血中的情况无关（p<0.01）。此外，PAR患者鼻粘膜中有相当比例的γδ T细胞合成白细胞介素-4（IL-4）和白细胞介素-5，但干扰素-γ（IFN-γ）的合成量可忽略不计。PAR患者鼻粘膜γδ T细胞不同亚群比例增加且活化，以及其Th2型细胞因子谱与自身外周血中的情况无关，这些观察结果表明寡克隆扩增的鼻粘膜γδ T细胞在PAR发病机制中起重要作用。
