Interferon-α Abrogates Tolerance Induction by Human Tolerogenic Dendritic Cells
Interferon-α Abrogates Tolerance Induction by Human Tolerogenic Dendritic Cells
复制标题
DOI：
10.1371/journal.pone.0022763
复制
发表时间：
2011-07-27
期刊：
影响因子：
3.7
通讯作者：
Steinbrink, Kerstin
中科院分区：
文献类型：
--
作者：
Bacher, Nicole;Graulich, Edith;Steinbrink, Kerstin
背景：据报道，干扰素- α (ifn - α)是恶性肿瘤如黑色素瘤和几种病毒感染的一种批准的辅助治疗方法。在恶性疾病中，耐受过程在肿瘤进展中起关键作用。本研究分析了ifn - α对人耐受性树突状细胞（DC）耐受性诱导的影响。我们专注于耐受性IL-10调节DC (IL-10 DC)，已知其可诱导无能调节性T细胞（iTregs）。方法/主要发现：ifn - α通过上调分化标记CD83和共刺激分子来促进IL-10 DC的成熟。与对照耐受性DC相比，ifn - α处理导致DC刺激T细胞活化的能力增加。我们观察到，在ifn - α -DC刺激下，T细胞增殖增强，CD4（+）和CD8(+) T细胞产生ifn - γ增加，表明在ifn - α存在下，耐受性DC的免疫原能力得到恢复。值得注意的是，再刺激实验显示，ifn - α处理耐受性DC可消除T细胞能量的诱导和iTregs的抑制功能。结论/意义：ifn - α通过逆转人DC的耐受性功能来抑制T细胞耐受的诱导。
Background: Administration of interferon-alpha (IFN-alpha) represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-alpha on tolerance induction by human tolerogenic dendritic cells (DC) was analyzed. We focussed on tolerogenic IL-10-modulated DC (IL-10 DC) that are known to induce anergic regulatory T cells (iTregs).Methodology/Principal Findings: IFN-alpha promoted an enhanced maturation of IL-10 DC as demonstrated by upregulation of the differentiation marker CD83 as well as costimulatory molecules. IFN-alpha treatment resulted in an increased capacity of DC to stimulate T cell activation compared to control tolerogenic DC. We observed a strengthened T cell proliferation and increased IFN-gamma production of CD4(+) and CD8(+) T cells stimulated by IFN-alpha-DC, demonstrating a restoration of the immunogenic capacity of tolerogenic DC in the presence of IFN-alpha. Notably, restimulation experiments revealed that IFN-alpha treatment of tolerogenic DC abolished the induction of T cell anergy and suppressor function of iTregs. In contrast, IFN-alphaConclusions/Significance: IFN-alpha inhibits the induction of T cell tolerance by reversing the tolerogenic function of human DC.