Transient depletion of CD4+ CD25+ regulatory T cells results in multiple autoimmune diseases in wild-type and B-cell-deficient NOD mice
Transient depletion of CD4+ CD25+ regulatory T cells results in multiple autoimmune diseases in wild-type and B-cell-deficient NOD mice
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DOI：
10.1111/imm.12065
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发表时间：
2013-06-01
期刊：
影响因子：
6.4
通讯作者：
Braley-Mullen, Helen
中科院分区：
文献类型：
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作者：
Ellis, Jason S.;Wan, Xiaoxiao;Braley-Mullen, Helen
大约80%的雌性野生型非肥胖糖尿病(WT NOD)小鼠自发发生糖尿病，而B细胞缺陷(B/)NOD小鼠对糖尿病具有抵抗力。B/B小鼠对其他自发和实验诱导的自身免疫性疾病也具有抵抗力，包括关节炎、系统性红斑狼疮、干燥综合征和甲状腺炎。在正常情况下，外周自身反应性T细胞的激活受到CD4+CD25+自然调节性T细胞(Treg)的限制。B/NOD.H-2H4小鼠通常对自发性自身免疫性甲状腺炎(SAT)具有抵抗力，当Treg细胞耗尽时会出现SAT，这表明当自身抗原最初由非B细胞抗原提呈细胞递呈时，Treg细胞优先被激活。为了验证B/小鼠中Treg细胞活性增加有助于它们对其他自身免疫性疾病的抵抗力这一假设，WT和B/NOD小鼠被给予抗CD25以瞬时耗尽CD4+CD25+Treg细胞。给予抗CD25抗体的WT和B/NOD小鼠发生糖尿病的时间比给予大鼠免疫球蛋白的WT小鼠要早得多，而给予大鼠免疫球蛋白的B/NOD小鼠没有发生糖尿病。与给予大鼠免疫球蛋白的对照组相比，缺乏Treg细胞的小鼠胰腺、唾液腺和甲状腺中的淋巴细胞渗透增加。这些结果与B细胞缺陷NOD小鼠对几种自身免疫性疾病的抵抗力是由于Treg细胞的活性的假设是一致的。
Approximately 80% of female wild-type non-obese diabetic (WT NOD) mice spontaneously develop diabetes, whereas B-cell-deficient (B/) NOD mice are resistant to diabetes. B/ mice are also resistant to other spontaneous and experimentally induced autoimmune diseases, including arthritis, systemic lupus erythematosus, Sjogren syndrome and thyroiditis. Under normal conditions, activation of self-reactive T cells in the periphery is limited by CD4+CD25+ natural regulatory T (Treg) cells. B/ NOD.H-2h4 mice, normally resistant to spontaneous autoimmune thyroiditis (SAT), develop SAT when Treg cells are depleted, suggesting that Treg cells are preferentially activated when autoantigen is initially presented by non-B-cell antigen-presenting cells. To test the hypothesis that increased Treg cell activity in B/ mice contributes to their resistance to other autoimmune diseases, WT and B/ NOD mice were given anti-CD25 to transiently deplete CD4+CD25+ Treg cells. The WT and B/ NOD mice given anti-CD25 developed diabetes much earlier than WT mice given rat IgG, whereas rat IgG-treated B/ mice did not develop diabetes. Treg-cell-depleted mice had increased lymphocyte infiltration of the pancreas, salivary glands and thyroid compared with controls given rat IgG. These results are consistent with the hypothesis that resistance of B-cell-deficient NOD mice to several autoimmune diseases is due to the activity of Treg cells.