Differential effect of neonatal thymectomy on systemic and organ-specific autoimmune disease
Differential effect of neonatal thymectomy on systemic and organ-specific autoimmune disease
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DOI：
10.1093/intimm/dxf105
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发表时间：
2002-12-01
影响因子：
4.4
通讯作者：
Tung, KSK
中科院分区：
文献类型：
--
作者：
Bagavant, H;Thompson, C;Tung, KSK
出生后第3天（d3 tx）的胸腺切除术耗尽了CD 4（+）CD 25（+）调节性T细胞，导致多种独立的器官特异性自身免疫性疾病。然而，系统性自身免疫性疾病，如系统性红斑狼疮还没有报告在d3 tx小鼠。在本文中，我们研究了d3 tx对狼疮易感（SWR x NZB）F-1（SNF 1）小鼠自发性自身抗体应答和免疫复合物肾小球肾炎（GN）的影响。d3 tx SNF 1小鼠对双链DNA和DNA-组蛋白复合物产生了加速的抗体反应，并且活化的CD 4（+）T细胞的频率增加。出乎意料的是，在d3 tx SNF 1小鼠中，GN的肾组织病理学和死亡率显著改善，同时表现出T（h）2偏倚的抗体应答。到16周，d3 tx小鼠的总IgG和自身抗原特异性IgG 1水平较高，在12个月时，自身抗原特异性IgG 2a显著低于假胸腺切除小鼠。这些差异与d3 tx小鼠肾洗脱液中总IgG和自身抗原特异性IgG 2a的减少相对应。此外，虽然所有小鼠的肾小球系膜和外周毛细血管袢中有免疫复合物沉积，但仅限于系膜区的IgG 2a和C3沉积在d3 tx小鼠中更常见。D3 tx SNF 1小鼠，免受狼疮样GN，发展器官特异性自身免疫反应和疾病，包括前列腺炎，睾丸炎和卵巢炎，以及前列腺，心脏和骨骼肌抗原的抗体。因此，d3 tx自相矛盾地保护SNF 1小鼠免受遗传倾向性狼疮样GN，但促进从头器官特异性自身免疫。
Thymectomy on day 3 after birth (d3tx) depletes CD4(+)CD25(+) regulatory T cells leading to multiple independent organ-specific autoimmune diseases. However, systemic autoimmune disease such as systemic lupus erythematosus has not been reported in d3tx mice. Herein, we investigate the effect of d3tx on spontaneous autoantibody response and immune complex glomerulonephritis (GN) in the lupus-prone (SWR x NZB)F-1 (SNF1) mice. The d3tx SNF1 mice developed accelerated antibody responses to double-stranded DNA and DNA-histone complexes, and an increased frequency of activated CD4(+) T cells. Unexpectedly, the renal histopathology and mortality from GN were significantly ameliorated in d3tx SNF1 mice, which concomitantly exhibited a T(h)2-biased antibody response. By 16 weeks, the d3tx mice had higher levels of total and autoantigen-specific IgG1, and at 12 months, the autoantigen-specific IgG2a was significantly below that of the sham thymectomized mice. These differences corresponded with reduction in total and autoantigen-specific IgG2a in the renal eluates of the d3tx mice. In addition, while all the mice had immune complex deposition in the mesangium and peripheral capillary loops of the glomeruli, IgG2a and C3 deposits restricted to the mesangial regions alone were more frequent in d3tx mice. D3tx SNF1 mice, protected from lupus-like GN, developed organ-specific autoimmune responses and diseases including prostatitis, orchitis and oophoritis, and antibodies to prostate, cardiac and skeletal muscle antigens. Therefore, d3tx paradoxically protects SNF1 mice from genetically prone lupus-like GN, yet promotes de novo organ-specific autoimmunity.