Etiological study of oral disease in HIV and HTLV-I positive patients-characteristics of salivary gland cells-

HIV和HTLV-I阳性患者口腔疾病的病因学研究-唾液腺细胞特征-

• 批准号: 10470435
• 负责人: ABE Kihachiro
• 金额: $ 9.28万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470435/
• 关键词: HIV; HTLV-I; autoimmune disease; Sjogren's syndrome; Salivary gland; cytokine; T cell; シェーグレン症侯群; パッチクランプ

Measurement of whole salivary flow rate revealed that function of salivary gland is frequently impaired in HIV- or HTLV-I-infected patients. The salivary gland dysfunction observed in these patients was clinically similar to one of autoimmune disease, Sjogren's syndrome. To clarify the etiopathological association of Sjogren's syndrome with HTLV-I, we first of all examined the localization of HTLV-I proviral DNA in the salivary gland of the patients. The results suggested HTLV-I infected T cells accumulate in the salivary glands and are involved in the induction of the salivary gland dysfunction. Cytokines detected in the salivary glands was mainly Th1 cytokines IL-2 and IFNγ produced by CD4-positive T cells. Furthermore, examination of the T cell receptor C gene usage in the salivary glands revealed that T cells expressing unique T cell receptors are accumulated in the salivary glands. These T cells were commonly present in patients with Sjogren's syndrome. These results strongly suggest that a self-reactive T cells could be infected with the virus, activated by the virus, and thereafter induce this type of autoimmune disease. Using a path-clamp method, we found, in rat salivary acinar cells, a K^+ channels which was Ca^<2+>-dependent and voltage-dependent. This report is the first report in the world.

全唾液流率测量显示，HIV或HTLV-I感染患者唾液腺功能经常受损。在这些患者中观察到的唾液腺功能障碍在临床上类似于自身免疫性疾病之一，干燥综合征。为了阐明干燥综合征与HTLV-I的病因病理联系，我们首先检测了HTLV-I前病毒DNA在患者唾液腺中的定位。提示HTLV-I感染的T细胞聚集在唾液腺中，并参与了唾液腺功能障碍的诱导。唾液腺中检测到的细胞因子主要是Th1型细胞因子IL-2和γ阳性T细胞产生的干扰素。此外，对唾液腺中T细胞受体C基因使用情况的检测显示，表达独特T细胞受体的T细胞聚集在唾液腺中。这些T细胞在干燥综合征患者中普遍存在。这些结果强烈地表明，自身反应性T细胞可能被病毒感染并被病毒激活，从而引发这种类型的自身免疫性疾病。用路径钳方法，我们在大鼠唾液腺泡细胞上发现一种钙依赖性和电压依赖性的K~(++)通道。这份报告是世界上第一份报告。

项目成果

M.Sasaki, S.Nakamura, Y.Ohyama, M.Shinohara, I.Ezaki, H.Hara, T.Kadena, K.Kishihara, K.Yamamoto, K.Nomoto and K.Shirasuna: "Accumulation of common T cell clonotypes in the salivary glands of patients with human T lymphotropic virus type I-associated and i

M.Sasaki、S.Nakamura、Y.Ohyama、M.Shinohara、I.Ezaki、H.Hara、T.Kadena、K.Kishihara、K.Yamamoto、K.Nomoto 和 K.Shirasuna：“普通 T 细胞的积累

Oyama Y. et al: "An accumulation of human t-lynophotrophic virus type I (HTLV-I)-intected T cells in the salivary glands of patients with HTLV-I-associated sjogren's synd-rome." Arthritis and Reumatism. 41. 1972-1978 (1998)

Oyama Y. 等人：“HTLV-I 相关干燥综合征患者唾液腺中感染人类 T 淋巴细胞病毒 I 型 (HTLV-I) 的 T 细胞积聚。”

Y.Ohyama, S.Nakamura, H.Hara, M.Shinohara, M.Sasaki, A.Hiroki, T.Mouri, S.Tunawaki, K.Abe, K.Shirasuna and K.Nomoto: "Accumulation of human T lymphotrophic virus type I-infected T cells in the salivary glands of patients with human T lymphotropic virus ty

Y.Ohyama、S.Nakamura、H.Hara、M.Shinohara、M.Sasaki、A.Hiroki、T.Mouri、S.Tunawaki、K.Abe、K.Shirasuna 和 K.Nomoto：“人类 T 淋巴细胞的积累

M.Sasaki et al: "Accumulation of common T cell clonotypes in the salivary glands of patients with human T lymphotropic virus type I-associated and ideopathic Sjogen's syndrome"J.of Immunology. 164. 2823-2831 (2000)

M.Sasaki 等人：“人类 T 淋巴细胞病毒 I 型相关和特发性 Sjogen 综合征患者唾液腺中常见 T 细胞克隆型的积累”《免疫学杂志》。

Y.Ohyama, et al.: "Accumulation of human T lymphotrophic virus type I-infected T cells in the salivary glands of patients with human T lymphotropic virus type I-associated Sjogren's syndrome."Arthritis & Rheumatism. 41(11). 1973-1978 (1998)

Y.Ohyama 等人：“人类 T 淋巴细胞病毒 I 型感染的 T 细胞在人类 T 淋巴细胞病毒 I 型相关干燥综合征患者的唾液腺中积累。”关节炎