利用骨髓樹突細胞研究全身性紅斑性狼瘡動物模式之自體反應性CD8+ T細胞的角色

Study on autoreactive CD8+ T cell proliferative response with bone marrow-derived dendritic cell in murine lupus

林宜萱(Yi-Shiuan Lin)

指導教授 ： 孫昭玲

高雄醫學大學/醫學院/醫學研究所/碩士(2007年)

https://doi.org/10.6832/KMU.2007.00153

摘要

前言：全身性紅斑性狼瘡( Systemic Lupus Erythematosus, SLE )的特徵是體內產生許多種自體抗體，而這些抗體主要是辨認細胞核內的完整結構，例如：nucleosome、histone及DNA等。已有研究顯示，在紅斑性狼瘡致病機轉中nucleosome為重要的自體抗原來源，且可能由凋亡細胞所提供，因為凋亡小體內可測到nucleosome的存在。然而，目前仍無直接證據證明紅斑性狼瘡病人體內凋亡細胞所提供之自體抗原能夠刺激自體反應性CD8+ T細胞的活化。因此本論文目的在觀察樹突細胞是否會處理和呈現凋亡細胞的抗原來活化自體反應性CD8+ T細胞，及自體反應性CD8+ T細胞在紅斑性狼瘡疾病中所扮演的角色。
實驗方法：實驗的設計主要是利用骨髓樹突細胞來吞噬histone peptides和凋亡細胞，觀察其可否藉由cross-priming的現象來刺激BWF1小鼠之CD8+ T細胞的活化增生。
結果：BWF1小鼠體內確實有一群自體反應性CD8+ T細胞的存在，且能夠辨認對紅斑性狼瘡致病很重要的histone peptide，這包括H2A11-30、H2A31-50、H2A41-60、H2A51-70、H2A61-80、H2A101-120、H2A111-130、H341-60、H361-80、H371-90、H381-100、H391-110、H3111-130、H3121-136；但H2B及H4 pepdide則無法刺激BWF1小鼠的CD8+ T細胞增生。
結論：目前我們正在確認是否凋亡小體經由骨髓樹突細胞吞噬處理後，也能夠活化BWF1小鼠的CD8+ T細胞，我們的研究能幫助釐清紅斑性狼瘡中CD8+ T細胞所扮演的角色。

關鍵字

樹突細胞 ； 全身性紅斑性狼瘡 ； CD8+T細胞 ； 凋亡細胞

並列摘要

Objectives. Systemic Lupus Erythematosus ( SLE ) is characterized by the existence of auto-antibodies against nuclear structures, such as nucleosomes, histone protein and DNA. Several studies have shown that apoptotic cells could provide a source of autoantigens during SLE initiation and progression. Nucleosomes can be presented on the surface of apoptotic bodies, while others accumulate inside apoptotic bodies. However, there is no direct evidence demonstrating that apoptotic cell provide self-antigens, such as histone, to stimulate autoreactive CD8+ T cells in lupus. The aim of this study was to examine that bone marrow-derived dendritic cells (BMDCs) could process and present self-antigens from apoptotic cells to induce the proliferation of autoreactive CD8+ T cells in murine lupus.
Methods. BMDCs were used to pulsed with histone peptides or apoptotic cells to stimulate the proliferative responses of CD8+ T cells from disease-developing NZB×NZW(BWF1) mice in vitro.
Results. The results of this study show that histone peptide pulsed BMDCs could stimulate the proliferative response of histone peptide-specific CD8+ T cells from BWF1 mice, including H2A11-30, H2A31-50, H2A41-60, H2A51-70, H2A61-80, H2A101-120, H2A111-130, H341-60, H361-80, H371-90, H381-100, H391-110, H3111-130 and H3121-136. H2B and H4 peptide could not stimulate the proliferation of CD8+ T cells from BWF1 mice.
Conclusion. We are now trying to examine whether BMDCs can process and present self-antigens from apoptotic cells to stimulate the proliferation of CD8+ T cells in BWF1 mice. Our study will help to understanding the role of autoreactive CD8+ T cells in murine lupus.

並列關鍵字

dendritic cell ； Systemic Lupus Erythematosus ； CD8+ T cell ； apoptotic cell ； histone peptide

參考文獻

1. Maddison, P. J. 2002. Is it SLE? Best Pract Res Clin Rheumatol 16:167.

2. Kotzin, B. L. 1996. Systemic lupus erythematosus. Cell 85:303.

3. Haq, I., and D. A. Isenberg. 2002. How does one assess and monitor patients with systemic lupus erythematosus in daily clinical practice? Best Pract Res Clin Rheumatol 16:181.

4. Tan, E. M. 1989. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol 44:93.

5. Tan, E. M., A. S. Cohen, J. F. Fries, A. T. Masi, D. J. McShane, N. F. Rothfield, J. G. Schaller, N. Talal, and R. J. Winchester. 1982. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271.