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

我们用双色流式细胞术检测了自身免疫性甲状腺疾病患者的血液和甲状腺中的淋巴细胞亚群，以确定导致桥本氏病和Graves病甲状腺组织分别发生刺激性和破坏性变化的免疫背景的差异。在活动期桥本病伴破坏性甲状腺功能亢进症患者外周血中，TGammadelta(CD3、TCRalphabeta、-TCRGammadelta)细胞和CD8细胞(包括细胞毒性T细胞)均减少，而CD5^B(CD5、CD19)细胞显著增加。在甲状腺中，桥本氏病和Graves病的细胞毒性T(CD8、CD11b)细胞和CD5~(-)-B(CD5、CD19~-)细胞的比例分别高于外周血。CD5^-B细胞、辅助性T细胞(CD4Leu8-)和生发中心T细胞(CD4CD57)比例较高，抑制性T细胞(CD4Leu8-)比例较高，…两种疾病患者外周血中抑制性T细胞(CD8、CD57或CD8、CD11b)和NK(CD16、CD57)细胞均低于外周血。TGammadelta细胞在血液和甲状腺中的分布相似。出乎意料的是，两种疾病的甲状腺组织中均存在双阴性T细胞(CD3^TCRalphabeta^&lt；/-&gt；TCRGammadelta^-CD4^-CD8^-)和双阳性T(CD4^CD8^-)细胞。此外，我们通过ELISPOT试验检测了哪个B细胞亚群能够产生甲状腺自身抗体。CD5~+B细胞产生Ig G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)。CD5^B和CD5^-B细胞在B细胞有丝分裂原刺激下，即使在正常人体内也能产生IgM类甲状腺自身抗体。这些结果提示：1)细胞毒性T细胞和CD5^B细胞分别在桥本病和Graves病的不同病理特征中起重要作用；2)甲状腺中调节性T细胞和NK细胞数量的失衡导致产生甲状腺自身抗体的CD5^-B细胞的增殖；3)甲状腺内双阴性T细胞(CD3^TCRalphabeta^&lt；/-&gt；CD4^-CD8^-)和双阳性T细胞(CD4^CD8^)可能与自身免疫性甲状腺疾病的发病有关。较少

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