ACTH enhancement of T-lymphocyte cytotoxic responses.

ACTH enhancement of T-lymphocyte cytotoxic responses.
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ACTH 增强 T 淋巴细胞的细胞毒性反应。

DOI:
10.1007/s10571-005-3972-8
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发表时间:
2005
影响因子:
4
通讯作者:
Smith,EricM
Smith,EricM
中科院分区:
医学3区
文献类型:
--
作者:
Johnson,EveW;HughesJr,ThomasK;Smith,EricM

文献摘要

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1. 促肾上腺皮质激素(ACTH)是最早发现的与白细胞受体结合并调节免疫反应的神经肽之一。一般ACTH抑制免疫反应,但某些功能可以增强。本研究旨在确定ACTH对细胞毒性t淋巴细胞反应的影响,以及参与细胞的成分和主要表型。ACTH对细胞毒性的作用是在体外测量的,在实验中使用之前在体内敏化的t淋巴细胞。然后将细胞与ACTH和携带适当刺激性主要组织相容性抗原的靶细胞一起培养。ACTH对原发性混合淋巴细胞反应没有显著影响,但在ACTH治疗2天后,ACTH可将继发性(记忆性)细胞毒性反应提高至100%。这种效应是效应细胞生成动力学的转变,因此acth处理的培养物在第2天表现出增强的细胞毒活性,而在第3天没有对照培养物的细胞毒活性达到最大值那么明显。ACTH还能抑制刀豆蛋白a刺激的t淋巴细胞有丝分裂。未成熟胸腺细胞有丝分裂受到的抑制大于成熟胸腺细胞。IFN-γ在培养物中升高的发现表明,ACTH可能通过直接细胞改变或与调节细胞因子协同作用等机制的组合来增强记忆细胞毒性反应。虽然皮质类固醇可能是最被认可的影响免疫功能的神经内分泌、应激激素,但我们的研究表明,其他神经内分泌因子如ACTH也直接影响免疫功能。
1. Corticotropin (ACTH) was one of the first neuropeptides shown to bind to receptors on leukocytes and modulate immune responses. Generally ACTH inhibits immune responses, but certain functions can be enhanced. The present study was performed to determine the effects of ACTH on cytotoxic T-lymphocyte responses, the components, and the major phenotypes of the participating cells.2. The action of ACTH on cytotoxicity was measuredin vitro, in assays utilizing T-lymphocytes that had been previously sensitizedin vivo. The cells were then cultured with ACTH and target cells bearing the appropriate stimulatory major histocompatiblity antigens.3. ACTH did not significantly affect a primary mixed lymphocyte reaction whereas it enhanced a secondary (memory) cytotoxic response up to 100% following 2 days of ACTH treatment. The effect was a shift in the kinetics of effector cell generation so that ACTH-treated cultures demonstrated an augmented cytotoxic activity on day 2, that was not as pronounced on day 3 as cytotoxic activity in control cultures became maximal. ACTH also inhibited Concanavalin A-stimulated T-lymphocyte mitogenesis. Immature thymocyte mitogenesis was inhibited more than that of mature thymocytes.4. The finding that IFN-γ was elevated in the cultures suggested that ACTH may enhance memory cytotoxic responses through a combination of mechanisms such as direct cell alterations or synergy with regulatory cytokines. While corticosteroids are probably the most recognized neuroendocrine, stress hormone to affect immune functions, our study illustrates that other neuroendocrine factors such as ACTH, also directly affect immune functions.