Sharma Rahul, Jarjour Wael N, Zheng Lingjie, Gaskin Felicia, Fu Shu Man, Ju Shyr-Te
Department of Medicine, Division of Rheumatology and Immunology, University of Virginia Health System, Charlottesville, VA 22908, USA.
J Autoimmun. 2007 Aug;29(1):10-9. doi: 10.1016/j.jaut.2007.04.001. Epub 2007 May 23.
Scurfy mice which lacks functional Foxp3 transcription factor and CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, spontaneously develop autoimmune responses against skin, lung, liver and tail. However, many organs/tissues are spared from autoimmune attack. Here, we demonstrate that scurfy mice contain dormant autoimmune T cells that induced new diseases such as sialoadenitis, dacryoadenitis, pancreatitis, gastritis, intestinal inflammation, colitis, and myositis in RAG-1 KO mice. Inflammation in as many as 12 organs/tissues was consistently induced in individual recipients with scurfy lymph node cells containing as few as 1.25 x 10(6) CD4(+) T cells. Moreover, transfer of the multiple organ autoimmune diseases could be suppressed by as little as 0.5 x 10(6) CD4(+)CD25(+) Treg cells, mediated by inhibiting autoimmune T-cell expansion. Our study provides evidence for the presence of a large repertoire of autoimmune lymphocytes against various organs/tissues in scurfy mice as well as Treg cells in B6 mice capable of suppressing the expansion of these autoimmune lymphocytes. Various conditions that control the expression of autoimmune T cells are discussed.
缺乏功能性Foxp3转录因子和CD4(+)CD25(+)Foxp3(+)调节性T(Treg)细胞的“头皮屑”小鼠会自发产生针对皮肤、肺、肝脏和尾巴的自身免疫反应。然而,许多器官/组织并未受到自身免疫攻击。在此,我们证明“头皮屑”小鼠含有休眠的自身免疫T细胞,这些细胞在RAG-1基因敲除小鼠中诱发了诸如涎腺炎、泪腺炎、胰腺炎、胃炎、肠道炎症、结肠炎和肌炎等新疾病。在含有低至1.25×10(6)个CD4(+) T细胞的“头皮屑”淋巴结细胞的个体受体中,多达12个器官/组织持续发生炎症。此外,通过抑制自身免疫T细胞的扩增,低至0.5×10(6)个CD4(+)CD25(+) Treg细胞就能抑制多器官自身免疫疾病的转移。我们的研究为“头皮屑”小鼠中存在针对各种器官/组织的大量自身免疫淋巴细胞以及B6小鼠中能够抑制这些自身免疫淋巴细胞扩增的Treg细胞提供了证据。文中还讨论了控制自身免疫T细胞表达的各种条件。