Study on lymphocyte subsets infiltrating the target organ in autoimmune diseases.

自身免疫性疾病靶器官浸润淋巴细胞亚群的研究。

• 批准号: 05670420
• 负责人: IWATANI Yoshinori
• 金额: $ 1.34万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670420/
• 关键词: Autoimmune disease; Infiltrating lymphocyte; Thyroid; Hashimoto's disease; Graves' disease; Aggravation; CD4^+CD8^+ cells; CD4^-CD8^- cells

We examined lymphocyte subsets in both blood and thyroid from patients with autoimmune thyroid disease by two-color flow cytometry to identify the difference in immunological background that allows the stimulative and destructive changes in thyroid tissue in Hashimoto's and Graves' diseases, respectively. In Peripheral blood, both Tgammadelta (CD3^+TCRalphabeta^-TCRgammadelta^+) cells and CD8^+ cells (which include cytotoxic T cells) decreased in active Hashimoto's disease with destructive thyrotoxicosis and CD5^+B (CD5^+CD19^+) cells increased markedly in active Graves' disease with stimulative thyrotoxicosis. In thyroid gland, proportions of cytotoxic T (CD8^+CD11b^-) cells and CD5^-B (CD5^+CD19^-) cells were higher in Hashimoto's and Graves' diseases, respectively, as compared with those in the peripheral blood. Proportions of CD5^-B cells, helper T (CD4^+Leu8^-) cells and germinal center T (CD4^+CD57^+) cells were higher and proportions of suppressor-inducer T (CD4^+Leu8^+) cells, … More suppressor T (CD8^+CD57^+ or CD8^+CD11b^+) cells, and NK (CD16^+CD57^+) cells were lower than in the blood in both diseases. Tgammadelta cells were present similarly in both blood and thyroid. Unexpectedly, double negative T (CD3^+TCRalphabeta^<+/->TCRgammadelta^-CD4^-CD8^-) cells and double positive T (CD4^+CD8^+) cells were present in thyroid tissues of both diseases. Furthermore, we examined which B cell subset produces thyroid autoantibodies by using ELISPOT assay. CD5^-B cells produced IgG classes of thyroid autoantibodies (thyroid microsomal antibodies and thyroglobulin antibodies). IgM classes of thyroid autoantibodies were produced by both CD5^+B and CD5^-B cells even in normal subjects, when stimulated by B cell mitogen. These findings suggest that 1) cytotoxic T cells and CD5^+B cells are important for the different pathological features in Hashimoto's and Graves' diseases, respectively, 2) an imbalance in the numbers of regulatory T cells and NK cells that had appeared in the thyroid resulted in the proliferation of CD5^-B cells, which produce thyroid autoantibodies, and 3) intrathyroidal double negative T (CD3^+TCRalphabeta^<+/->CD4^-CD8^-) and double positive T (CD4^+CD8^+) cells may be related to the pathogenesis of autoimmune thyroid disease. Less

我们通过双色流式细胞术检测了自身免疫性甲状腺疾病患者血液和甲状腺中的淋巴细胞亚群，以确定桥本氏病和Graves病甲状腺组织中刺激性和破坏性变化的免疫背景差异。在外周血中，活动性桥本病伴破坏性甲状腺毒症患者T γ δ（CD 3 ^+ TCR α ^-TCR γ δ ^+）细胞和CD 8 ^+细胞（包括细胞毒性T细胞）均减少，而活动性Graves病伴刺激性甲状腺毒症患者CD 5 ^+B（CD 5 ^+ CD 19 ^+）细胞显著增加。在甲状腺中，与外周血相比，桥本氏病和Graves病患者的细胞毒性T（CD 8 ^+ CD 11b ^-）细胞和CD 5 ^-B（CD 5 ^+ CD 19 ^-）细胞的比例分别较高。CD 5 ^-B细胞、辅助性T（CD 4 ^+ Leu 8 ^-）细胞和生殖中心T（CD 4 ^+ CD 57 ^+）细胞的比例较高，抑制诱导性T（CD 4 ^+ Leu 8 ^+）细胞的比例较高， ...更多信息 在这两种疾病中，抑制性T（CD 8 ^+ CD 57 ^+或CD 8 ^+ CD 11b ^+）细胞和NK（CD 16 ^+ CD 57 ^+）细胞的含量均低于血液中的水平。T γ δ细胞在血液和甲状腺中的存在相似。出乎意料的是，在两种疾病的甲状腺组织中均存在双阴性T（CD 3 ^+ TCR α ^<+/-> TCR γ δ ^-CD 4 ^-CD 8 ^-）细胞和双阳性T（CD 4 ^+ CD 8 ^+）细胞。此外，我们用ELISPOT检测哪一个B细胞亚群产生甲状腺自身抗体。CD 5 ^-B细胞产生IgG类甲状腺自身抗体（甲状腺微粒体抗体和甲状腺球蛋白抗体）。即使在正常受试者中，当受到B细胞有丝分裂原刺激时，CD 5 ^+B和CD 5 ^-B细胞也会产生甲状腺自身抗体的IgM类。这些发现表明：1）细胞毒性T细胞和CD 5 ^+B细胞分别对桥本病和Graves病的不同病理特征很重要; 2）甲状腺中出现的调节性T细胞和NK细胞数量失衡导致产生甲状腺自身抗体的CD 5 ^-B细胞增殖，甲状腺内双阴性T细胞（CD 3 ^+ TCR α ^<+/-> CD 4 ^-CD 8 ^-）和双阳性T细胞（CD 4 ^+ CD 8 ^+）可能与自身免疫性甲状腺疾病的发病有关。少

项目成果

Iwatani, Y., Amino, N.: "Cellular immune abnormalities in autoimmune thyroid disease." Pathophysiology. 1 (S). 368- (1994)

Iwatani, Y., Amino, N.：“自身免疫性甲状腺疾病中的细胞免疫异常。”

Y.IWATANI et al.: "Intrathyroidal lymphocyte subsets,including unusual CD4^+CD8^+ cells and CD3^<10>TCRαβ^<101->CD4^-CD8^- cells,in autoimmune thyroid disease." Clinical and Experimental Immunology. 93. 430-436 (1993)

Y.IWATANI 等人：“自身免疫性甲状腺疾病中的甲状腺内淋巴细胞亚群，包括异常的 CD4^+CD8^+ 细胞和 CD3^<10>TCRαβ^<101->CD4^-CD8^- 细胞。”免疫学。93。430-436（1993）

Iwatani,Y.,Amino,N.: "Cellular immune abnormalities in autoimmune thyroid disease." Pathophysiology. 1(S). 368 (1994)

Iwatani,Y.,Amino,N.：“自身免疫性甲状腺疾病中的细胞免疫异常。”

Iwatani, Y., Hidaka, Y., Matsuzuka, F., Kuma, K., Amino, N.: "Intrathyroidal lymphocyte subsets, including unusual CD4^+CD8^+ cells and CD3^<10>TCRalphabeta^<10/->CD4^-CD8^- cells, in autoimmune thyroid disease." Clin.Exp.Immunol.93. 430-436 (1993)

Iwatani, Y.、Hidaka, Y.、Matsuzuka, F.、Kuma, K.、Amino, N.：“甲状腺内淋巴细胞亚群，包括异常 CD4^ CD8^ 细胞和 CD3^<10>TCRalphabeta^<10/->

Iwatani,Y.,et al.: "Intrathyroidal lyphocyte subsets,including unusual CD4^+CD8^+ cells and CD3^<1o>TCRαβ^<1o/->CD4^-CD8^- cells,in autoimmune thyroid disease." Clinical and Experimental Immunology. 93. 430-436 (1993)

Iwatani, Y., et al.：“自身免疫性甲状腺疾病中的甲状腺内淋巴细胞亚群，包括不寻常的 CD4^+CD8^+ 细胞和 CD3^<1o>TCRαβ^<1o/->CD4^-CD8^- 细胞。”临床和实验免疫学。93。430-436（1993）