Regulation of CD40L expression on natural killer cells by interleukin-12 and interferon γ: its role in the elicitation of an effective antitumor immune response
Regulation of CD40L expression on natural killer cells by interleukin-12 and interferon γ: its role in the elicitation of an effective antitumor immune response
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白介素12和干扰素γ对自然杀伤细胞CD40L表达的调节：其在引发有效抗肿瘤免疫反应中的作用
DOI：
10.1007/s002620000151
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
A. Khar
中科院分区：
文献类型：
--
作者：
M. Jyothi;A. Khar
摘要效应细胞的功能受多种积极信号的调节，参与抗肿瘤免疫的调节。CD40和CD40配体(CD40L)的相互作用参与了有效的细胞介导和体液免疫反应的产生，其中细胞因子在这些分子的表达中起着重要作用。我们早期的研究表明，移植到S.C.的大鼠组织细胞瘤自发消退。是由CD8+CD3−NK细胞介导的。CD40-CD40L在肿瘤消退过程中的调节作用是很有意义的。与正常动物的细胞相比，肿瘤移植动物的自然杀伤细胞(NK)和T细胞上CD40L的表达增强。皮下注射可诱导AK-5肿瘤细胞表面CD40的表达。移植。抗IL-12(抗IL-12)和抗干扰素γ(抗干扰素γ)抗体可下调NK和T细胞表面CD40L的表达，同时抑制NK细胞的细胞毒活性、细胞因子的释放和抗肿瘤抗体的产生。幼稚NK细胞与固定的AK-5细胞共培养后，可诱导表达CD40L。CD40L的表达调节了NK细胞的免疫应答，部分是通过激活核因子kB(NF-kB)。此外，通过抗CD40L抗体介导的CD40L信号通路可促进肿瘤移植动物NK细胞的细胞毒作用和核因子-kB结合活性。提示在AK-5肿瘤消退过程中，效应细胞CD40L的表达受IL-12和干扰素γ的调节，并能有效地调节NK细胞介导的免疫应答。
Abstract Effector cell functions are regulated by a number of positive signals for the mediation of antitumor immunity. The CD40 and CD40 ligand (CD40L) interaction has been implicated in the generation of effective cell-mediated and humoral immune responses, where cytokines have been shown to play a significant role in the expression of these molecules. Our earlier studies have shown that spontaneous regression of a rat histiocytoma transplanted s.c. is mediated by CD8+ CD3− NK cells. The CD40-CD40L mediation during tumor regression was of interest. Tumor-transplanted animals showed enhanced expression of CD40L on natural killer (NK) and T cells, when compared to cells from normal animals. CD40 expression on AK-5 tumor cells was also induced after s.c. transplantation. Administration of anti-(interleukin-12) (anti-IL-12) and anti-(interferon γ) (anti-IFNγ) antibodies in tumor-bearing animals showed down-regulation of the expression of CD40L on NK and T cells with simultaneous inhibition of cytotoxic acitivity of NK cells, cytokine release and the production of antitumor antibody. Naive NK cells, when co-cultured with fixed AK-5 cells, were induced to express CD40L. CD40L expression modulated the immune response exerted by NK cells, in part by the activation of nuclear factor kB (NF-kB). Furthermore, the signaling via CD40L through the use of anti-CD40L antibody promoted the in vitro activation of cytotoxic as well as NF-kB binding activity in NK cells from tumor-transplanted animals. These observations demonstrate that the expression of CD40L by the effector cells is regulated by IL-12 and IFNγ, and could effectively modulate the NK-cell-mediated immune response during the regression of AK-5 tumor.