T cells in the myenteric plexus of achalasia patients show a skewed TCR repertoire and react to HSV-1 antigens
T cells in the myenteric plexus of achalasia patients show a skewed TCR repertoire and react to HSV-1 antigens
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DOI：
10.1111/j.1572-0241.2008.01956.x
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发表时间：
2008-07-01
影响因子：
9.8
通讯作者：
Zaninotto, Giovanni
中科院分区：
文献类型：
--
作者：
Facco, Monica;Brun, Paola;Zaninotto, Giovanni
目的：贲门失弛缓症是一种食管运动障碍，其特征是食管下括约肌（LES）肌间神经元的缺失。由于淋巴细胞浸润的存在表明免疫介导的机制正在进行的疾病的网站，我们研究了T细胞受体（TCR）的剧目和识别人类疱疹病毒1型（HSV-1）抗原的LES浸润T淋巴细胞在贲门失弛缓症patients.METHODS：59例特发性贲门失弛缓症和38个心脏跳动的尸体多器官供体（对照）进行了研究。结果：贲门失弛缓症患者食管淋巴细胞浸润程度明显高于对照组（P <0.05），贲门失弛缓症患者食管淋巴细胞浸润程度明显高于对照组（P <0.05），贲门失弛缓症患者食管淋巴细胞浸润程度明显高于对照组（P <0.05（分别为24.71% +/- 3.11和9.54% +/- 1.34; P < 0.05），以CD 3（+）CD 8（+）T细胞为主。对CD 3（+）细胞TCR β链库的表征显示，TCR β可变（BV）基因家族的表达数量有限（26个中的2 - 5个），具有高度限制性的谱，表明T细胞的疾病相关寡克隆选择。此外，贲门失弛缓症LES的淋巴细胞在体外对暴露于HSV-1抗原有特异性反应，表现为增殖增加和Th-1型细胞因子释放增加。这些数据表明，贲门失弛缓症患者LES内的寡克隆淋巴细胞浸润可能代表HSV-1抗原触发的免疫炎症反应的痕迹，而Th 1-Th 2细胞在LES内的表达可能与HSV-1抗原的表达有关。由活化的淋巴细胞释放的I型细胞因子可能有助于建立解释特发性贲门失弛缓症临床特征的神经元损伤。
OBJECTIVE: The loss of myenteric neurons in the lower esophageal sphincter (LES) characterizes achalasia, an esophageal motor disorder. Because the presence of lymphocytic infiltrates suggests an immuno-mediated mechanism ongoing at the sites of disease, we investigated the T-cell receptor (TCR) repertoire and the ability to recognize human herpes virus type 1 (HSV-1) antigens of LES-infiltrating T lymphocytes in achalasia patients.METHODS: Fifty-nine patients with idiopathic achalasia and 38 heart-beating cadaveric multiorgan donors (controls) were studied. By flow cytometry evaluation and CDR3 length spectratyping analysis, the lymphocytes of 18 patients and 15 controls were analyzed, whereas 41 patients and 23 controls were employed for functional assays.RESULTS: Achalasia patients were characterized by a significantly higher esophagus lymphocytic infiltrate than controls (24.71% +/- 3.11 and 9.54% +/- 1.34, respectively; P < 0.05), mainly represented by CD3(+)CD8(+) T cells. The characterization of TCR beta chain repertoire of CD3(+) cells showed the expression of a limited number of TCR beta variable (BV) gene families (from two to five out of 26), with highly restricted spectratypes, suggesting a disease-associated oligoclonal selection of T cells. Furthermore, lymphocytes from achalasia LES specifically responded to exposure to HSV-1 antigens in vitro as showed by increased proliferation and Th-1 type cytokines release.CONCLUSIONS: These data suggest that the oligoclonal lymphocytic infiltrate within the LES of achalasia patients may represent the trace of an immune-inflammatory reaction triggered by HSV-1 antigens and that the Th1-type cytokines released by the activated lymphocytes may contribute to establish the neuronal damage accounting for the clinical features of idiopathic achalasia.