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基于咪唑的化合物2-乙酰基-4-四羟基丁基咪唑可抑制成熟T细胞从胸腺迁出。

Emigration of mature T cells from the thymus is inhibited by the imidazole-based compound 2-acetyl-4-tetrahydroxybutylimidazole.

作者信息

Gugasyan R, Coward A, O'Connor L, Shortman K, Scollay R

机构信息

Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, NSW, Australia.

出版信息

Immunology. 1998 Mar;93(3):398-404. doi: 10.1046/j.1365-2567.1998.00434.x.

Abstract

The primary role of the thymus is to provide mature T cells for the peripheral immune system. The mechanisms involved in the cellular export processes are as yet unknown. In this study, we examined the ability of 2-acetyl-4-tetrahydroxybutylimidazole (THI), an agent widely used as a component of ammonia caramel food colouring, to inhibit T-cell export from the thymus. BALB/c mice were maintained on drinking water containing THI for 5 days. The mice showed a twofold increase in the total number of mature medullary thymocytes (CD4+CD8- and CD4-CD8+) as well as a slight decrease in the total number of immature double-positive cells (CD4+CD8+). The mature single-positive thymocytes were found to express high levels of the homing molecule L-selectin, suggesting that these potential emigrants were prevented from leaving the thymus. To confirm this, THI-treated mice were injected intrathymically with fluorescein isothiocyanate and the number of labelled T cells appearing in the lymph nodes and spleen was determined 16 hr later. A 10-fold decrease in the number of CD4+ and CD8+ recent thymic emigrants in the lymph nodes and spleen of THI-treated mice was observed. Previous studies have shown that THI does not affect other aspects of thymocyte development, such as proliferation and differentiation. Taken together, these results suggest that the immunosuppressive effects of THI may be due, in part, to preventing of the final step of T-cell export out of the thymus.

摘要

胸腺的主要作用是为外周免疫系统提供成熟的T细胞。细胞输出过程所涉及的机制尚不清楚。在本研究中,我们检测了2-乙酰基-4-四羟基丁基咪唑(THI)抑制胸腺T细胞输出的能力,THI是一种广泛用作氨焦糖食用色素成分的物质。将BALB/c小鼠置于含THI的饮用水中饲养5天。小鼠成熟髓质胸腺细胞(CD4+CD8-和CD4-CD8+)总数增加了两倍,而未成熟双阳性细胞(CD4+CD8+)总数略有减少。发现成熟的单阳性胸腺细胞表达高水平的归巢分子L-选择素,这表明这些潜在的迁出细胞被阻止离开胸腺。为了证实这一点,给经THI处理的小鼠胸腺内注射异硫氰酸荧光素,并在16小时后测定出现在淋巴结和脾脏中的标记T细胞数量。观察到经THI处理的小鼠淋巴结和脾脏中CD4+和CD8+近期胸腺迁出细胞数量减少了10倍。先前的研究表明,THI不影响胸腺细胞发育的其他方面,如增殖和分化。综上所述,这些结果表明,THI的免疫抑制作用可能部分归因于阻止T细胞从胸腺输出的最后一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62ab/1364089/b9dfc22d3137/immunology00047-0098-a.jpg

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