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首页> 美国卫生研究院文献>Clinical and Experimental Immunology >Pathogenic mechanisms in murine autoimmune thyroiditis: short- and long-term effects of in vivo depletion of CD4+ and CD8+ cells.
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Pathogenic mechanisms in murine autoimmune thyroiditis: short- and long-term effects of in vivo depletion of CD4+ and CD8+ cells.

机译：鼠自身免疫性甲状腺炎的致病机制：体内消耗CD4 +和CD8 +细胞的短期和长期影响。

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Both murine CD4+ and CD8+ cells are found in the thyroid infiltrate in experimental autoimmune thyroiditis (EAT) induced with mouse thyroglobulin (MTg). MTg activation of immune cells in vitro enables CD4+ cells to transfer thyroiditis adoptively and to aid the cytotoxic capacity of CD8+ cells for thyroid monolayers. To dissect their relative contribution to pathogenesis in vivo, depleting doses of paired rat monoclonal antibodies (MoAb) recognizing two distinct CD4 or CD8 epitopes were injected alone or in combination. Early treatment with CD4 MoAb interfered with the induction and development of EAT, whereas similar treatment with CD8 MoAb reduced infiltration moderately and did not enhance antibody response. To examine the long-term effect of therapy on advancing EAT, administration of MoAb was delayed to days 21 and 25, and thyroids were analysed immunohistochemically on days 28 and 70. Whereas control mice showed about 30% CD4+ and CD8+ cells at a 2:1 ratio (the remainder being mostly macrophages) on both days 28 and 70, the CD4 therapy regime led to reduced severity and the lesions on day 70 contained very low percentage of CD4+ cells, but elevated percentage of CD8+ cells (ratio 1:3.5). The CD8 therapy regime led to reduced CD8+ cells without changing the range of CD4+ cells (ratio 4:1). Thus, subset involvement may be influenced by the MoAb used. When CD4 and CD8 MoAb were combined, greater than 50% of the thyroids were cleared of all inflammatory cells; lesions when found were very small and contained less than 10% T cells (ratio 1:1). Since emerging T cells were not retained in the thyroid despite ongoing antigenic stimulus leading to increased antibody titres, the therapeutic effect of MoAb, even at an advanced stage of disease, was long lasting.
机译：在小鼠甲状腺球蛋白（MTg）诱导的实验性自身免疫性甲状腺炎（EAT）的甲状腺浸润液中，发现了小鼠CD4 +和CD8 +细胞。体外免疫细胞的MTg激活使CD4 +细胞过继转移甲状腺炎，并有助于CD8 +细胞对甲状腺单层细胞的细胞毒性作用。为了剖析它们对体内发病机理的相对贡献，将识别两个不同CD4或CD8表位的耗尽剂量的成对大鼠单克隆抗体（MoAb）单独注射或联合注射。 CD4 MoAb的早期治疗会干扰EAT的诱导和发展，而CD8 MoAb的类似治疗会适度降低浸润，并且不会增强抗体应答。为了检查治疗对进食EAT的长期影响，将MoAb的给药延迟至第21和25天，并在第28和70天对甲状腺进行免疫组织化学分析。而对照小鼠在2时显示约30％的CD4 +和CD8 +细胞在第28天和第70天，比率为1（其余大部分为巨噬细胞），CD4治疗方案导致严重程度降低，第70天的病变中CD4 +细胞的百分比非常低，而CD8 +细胞的百分比却很高（比例1：3.5） 。 CD8治疗方案可减少CD8 +细胞，而不会改变CD4 +细胞的范围（比例4：1）。因此，子集的参与可能会受到所用MoAb的影响。当CD4和CD8 MoAb合并使用时，超过50％的甲状腺清除了所有炎症细胞。发现的病灶非常小，并且含有少于10％的T细胞（比率1：1）。尽管持续的抗原刺激导致抗体滴度增加，但由于新兴的T细胞并未保留在甲状腺中，因此即使在疾病的晚期，MoAb的治疗效果也能持久。

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