探討自體免疫傾向之介白素15受器alpha鍵基因剔除小鼠之中心及周邊免疫耐受性

Study of Central and Peripheral Tolerance in the Autoimmune Prone Interleukin-15 Receptor α Chain Gene Knockout mice

蔡明翰(Ming-Han Tsai)

指導教授 ： 廖南詩 ； 張子文 ； 潘榮隆

國立清華大學/生命科學院/生物科技研究所/碩士(2006年)

https://doi.org/10.6843/NTHU.2006.00527

摘要

介白素15號受器(interleukin-15 receptor; IL-15R)是由α、β和γ鍵所組成。其中IL-15受器α鍵本身對IL-15具有高度的親和力，然而β和γ鍵受器則是對IL-15和介白素2號(Interleukin-2; IL-2)皆具有中度的親和力。之前的研究指出在IL-2受器α鍵，IL-2/IL-15受器β鍵，或IL-2之基因剔除之小鼠會產生早期且嚴重性的自體免疫反應，然而，這些症狀卻未曾在IL-15受器α鍵基因缺損之小鼠上發現。我們之前已在IL-15受器α鍵基因剔除，且年齡大於六個月之成年母鼠發現類紅斑性狼瘡症狀，卻不曾發現於野生型的對照組。在這篇論文裡，我證實了IL-15受器α鍵基因剔除的小鼠在胸線及周邊組織表現較差的免疫耐受性。這些結果可能提供了構成成年IL-15受器α鍵基因缺損小鼠產生自體免疫疾病的一些條件，因為其較差的免疫耐受性會造成自體反應的T細胞累積，進而造成自體免疫疾病。

關鍵字

介白素15 ； 介白素2 ； 介白素15受器 ； 自體免疫 ； 胸線負選擇 ； 紅斑狼瘡 ； 自體抗體 ； 胸線細胞 ； CD4輔助T細胞

並列摘要

Interleukin-15 receptor (IL-15R) contains α, β and γ chains. The α chain by itself binds to IL-15 with high affinity, while β and γ chains are intermediate affinity receptors for both Interleukin-2 (IL-2) and IL-15. Previous studies showed that mice deficient of IL-2 receptor α (IL-2Rα), IL-2/15 receptor β (IL-2/15Rβ) or IL-2 developed early progressing severe autoimmune diseases, a phenotype not observed in IL-15Rα knockout (IL-15Rα-/-) mice. We found that the Systemic Lupus Erythematosus (SLE)-like symptoms in female IL-15Rα-/- aged female mice older than 6 months but not in wild type (WT) counterpart. In this thesis, I demonstrated that IL-15Rα-/- mice exhibited inefficient tolerance in the thymus and in the periphery. These results may provide the mechanisms underlying the progressing autoimmune diseases in aged IL-15Rα-/- mice, which is the accumulation of autoimmune T cells resulted from inefficient immune tolerance.

並列關鍵字

Interlerkin-15 ； Interleukin-2 ； Interleukin-15R ； Autoimmunity ； Thymocyte negative selection ； Lupus ； Autoantibodies ； Thymocytes ； CD4+ T cells

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