Effects of nicotine exposure on T cell development in fetal thymus organ culture: Arrest of T cell maturation
Effects of nicotine exposure on T cell development in fetal thymus organ culture: Arrest of T cell maturation
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DOI：
10.4049/jimmunol.169.6.2915
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发表时间：
2002-09-15
影响因子：
4.4
通讯作者：
DeLuca, D
中科院分区：
文献类型：
--
作者：
Middlebrook, AJ;Martina, C;DeLuca, D
有证据表明，天然神经递质乙酰胆碱的生理功能和植物生物碱尼古丁的药理作用对免疫系统的发育和功能都有影响。研究了连续暴露于尼古丁超过12天的胎儿胸腺器官培养（FTOC）过程中的影响，并通过流式细胞术分析了胸腺细胞。在非常低浓度的尼古丁存在下，产生更多的未成熟T细胞（由低或阴性TCR表达定义）和更少的成熟T细胞（TCR的中等或高表达）。此外，表达CD 69的细胞数量增加，在较小程度上，表达CD 95（Fas）。当将来自较年轻（妊娠13-14天）幼仔的胎仔胸腺叶用于FTOC时，发生了这些效应。如果FTOC是使用年龄较大（妊娠15-16天）的幼仔组织建立的，尼古丁几乎没有影响，这表明它可能只对未成熟的T细胞前体起作用。与未成熟细胞的增加一致，重组酶激活基因的表达被发现升高。尼古丁的作用被部分阻断，同时加入烟碱拮抗剂d-筒箭毒碱。此外，单独使用d-筒箭毒碱可以阻止未成熟和成熟小鼠胸腺细胞的发育，这表明存在一种内源性配体，该配体可能与发育中的胸腺细胞上的尼古丁乙酰胆碱受体结合，并影响正常胸腺个体发育的过程。
There is evidence for both physiological functions of the natural neurotransmitter, acetylcholine, and pharmacological actions of the plant alkaloid, nicotine, on the development and function of the immune system. The effects of continuous exposure to nicotine over a 12-day course of fetal thymus organ culture (FTOC) were studied, and thymocytes were analyzed by flow cytometry. In the presence of very low concentrations of nicotine many more immature T cells (defined by low or negative TCR expression) and fewer mature T cells (intermediate or high expression of TCR) were produced. In addition, the numbers of cells expressing CD69 and, to a lesser extent, CD95 (Fas) were increased. These effects took place when fetal thymus lobes from younger (13-14 days gestation) pups were used for FTOC. If FTOC were set up using tissue from older (15-16 days gestation pups), nicotine had little effect, suggesting that it may act only on immature T cell precursors. Consistent with an increase in immature cells, the expression of recombinase-activating genes was found to be elevated. Nicotine effects were partially blocked by the simultaneous addition of the nicotinic antagonist d-tubocurarine. Furthermore, d-tubocurarine alone blocked the development of both immature and mature murine thymocytes, suggesting the presence of an endogenous ligand that may engage nicotinic acetylcholine receptors on developing thymocytes and influence the course of normal thymic ontogeny.