IFN-α2b Reduces IL-2 Production and IL-2 Receptor Function in Primary CD4+ T Cells
IFN-α2b Reduces IL-2 Production and IL-2 Receptor Function in Primary CD4+ T Cells
复制标题
IFN-α2b 减少原代 CD4+ T 细胞中 IL-2 的产生和 IL-2 受体功能
作者：
D. Zella;F. Romerio;S. Curreli;P. Secchiero;C. Cicala;D. Zagury;R. Gallo
干扰素-α最初被描述为一种抗病毒细胞因子，后来被证明影响几种细胞功能，包括细胞分化和增殖。由于这些原因，干扰素-α目前被用于治疗病毒感染和恶性肿瘤的临床实践。在这篇手稿中，我们展示了两种新的机制，同时负责干扰素-α的抗增殖作用。首先，长期使用干扰素-α治疗的原代CD_4+T细胞减少了CD3和CD_(28)的表面表达。这些事件导致丝裂原激活的胞外信号调节激活激酶及其底物胞外信号调节激酶的磷酸化降低，导致IL-2的产生减少。第二，干扰素-α处理原代CD_4+T细胞，通过显著降低IL-2R复合体的关键成分α链的合成和表面表达，降低了对外源性IL-2刺激的增殖反应。这些结果可能与干扰素-α的抗肿瘤作用有关，并可能帮助我们更好地了解它在抑制艾滋病毒感染者大部分CD_4+T细胞(未感染细胞)增殖方面的不利作用，众所周知，艾滋病毒感染者会过度产生干扰素-α。
Initially described as an antiviral cytokine, IFN-α has been subsequently shown to affect several cellular functions, including cellular differentiation and proliferation. For these reasons, IFN-α is currently used in clinical practice for the treatment of viral infections and malignancies. In this manuscript, we show two novel mechanisms concomitantly responsible for the antiproliferative effect of IFN-α. First, long-term treatment with IFN-α of primary CD4+ T cells reduced surface expression of CD3 and CD28. These events resulted in decreased phosphorylation of the mitogen-activated extracellular signal-regulated activating kinase and its substrate extracellular signal-regulated kinase, leading to diminished production of IL-2. Second, IFN-α treatment of primary CD4+ T cells reduced proliferative response to stimulation in the presence of exogenous IL-2 by markedly decreasing mRNA synthesis and surface expression of CD25 (α-chain), a critical component of the IL-2R complex. These results may be relevant for the antitumor effects of IFN-α and may help us to better understand its detrimental role in the inhibition of proliferation of the bulk of CD4+ T cells (uninfected cells) in HIV-infected persons, who are known to overproduce IFN-α.
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影响因子：
11.2
作者：
L. Pfeffer;C. Dinarello;R. Herberman;B. Williams;E. Borden;R. Bordens;M. Walter;T. L. Nagabhushan;P. Trotta;S. Pestka
通讯作者：
L. Pfeffer;C. Dinarello;R. Herberman;B. Williams;E. Borden;R. Bordens;M. Walter;T. L. Nagabhushan;P. Trotta;S. Pestka
影响因子：
3.3
作者：
GARDNER, AM;VAILLANCOURT, RR;JOHNSON, GL
通讯作者：
JOHNSON, GL
影响因子：
56.9
作者：
Darnell, JE
通讯作者：
Darnell, JE
影响因子：
56.9
作者：
MOODIE, SA;WILLUMSEN, BM;WOLFMAN, A
通讯作者：
WOLFMAN, A
T 细胞中的细胞外信号调节激酶。
DOI：
--
发表时间：
1992
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Whitehurst,CE;Boulton,TG;Cobb,MH;Geppert,TD
通讯作者：
Geppert,TD