Dendritic cells activated by an anti-inflammatory agent induce CD4(+) T helper type 2 responses without impairing CD8(+) memory and effector cytotoxic T-lymphocyte responses.
Dendritic cells activated by an anti-inflammatory agent induce CD4(+) T helper type 2 responses without impairing CD8(+) memory and effector cytotoxic T-lymphocyte responses.
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抗炎剂激活的树突状细胞可诱导 CD4( ) T 辅助细胞 2 型反应，而不损害 CD8( ) 记忆和效应细胞毒性 T 淋巴细胞反应。
DOI：
10.1111/j.1365-2567.2009.03193.x
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发表时间：
2010
期刊：
影响因子：
6.4
通讯作者：
Harn,DonaldA
中科院分区：
文献类型：
--
作者：
Wang,Yang;Da'Dara,AkramA;Thomas,PaulG;Harn,DonaldA
在发达国家人口中，促炎性疾病的患病率正在上升。这些疾病的增加推动了对新的免疫抑制、抗炎疗法的探索，这些疗法不会影响或最小地影响CD4+和/或CD8+T细胞介导的免疫。本研究的目的是确定抗炎寡糖LNFP III(LNFP III)激活的抗原提呈细胞(APC)是否具有驱动CD4+T辅助细胞(Th)或CD8+记忆和效应性T细胞反应的能力受损。为了研究这一点，我们用LNFPIII激活了脾树突状细胞(SDCs)，并与脂多糖(LPS)刺激的SDCs进行了比较，检测了它们驱动抗原特异性CD4+Th、CD8+记忆和细胞毒性T细胞(CTL)反应的能力。LNFPIII激活的SDCs与脂多糖刺激的SDCs相比，共刺激分子的表达发生了变化，而两种化合物激活后SDC趋化因子的水平相似。LNFP III激活的SDCs产生的IL-12水平显著低于LPS激活的SDCs，而产生的IL-6水平却出人意料地高于LPS激活的SDCs。与以前使用骨髓来源的DC的研究类似，LNFP III激活的SDCs在活体中诱导了强烈的Th2反应。APC的LNFP III激活不依赖于Toll-IL-1受体适配器髓系分化因子88。重要的是，LNFPⅢ成熟的DC诱导CD8+记忆和效应性CTL反应，包括产生干扰素γ的CD8+T细胞的频率和CTL效应器的诱导。抗炎多糖LNFPIII治疗APC不会损害它们驱动CD8+效应器和记忆细胞介导的免疫的能力。
Prevalence of pro‐inflammatory diseases is rising in developed country populations. The increase in these diseases has fuelled the search for new, immune suppressive, anti‐inflammatory therapies, which do not impact, or minimally impact, CD4+and/or CD8+T‐cell‐mediated immunity. The goal of this study was to determine if antigen‐presenting cells (APCs) activated by the anti‐inflammatory oligosaccharide, lacto‐N‐fucopentaose III (LNFPIII), would have an impaired ability to drive CD4+T helper (Th) or CD8+memory and effector T‐cell responses. To investigate this we activated splenic dendritic cells (SDCs) with LNFPIII and examined their ability to drive antigen‐specific CD4+Th, and CD8+memory and cytotoxic T‐cell (CTL) responses compared with lipopolysaccharide (LPS) ‐stimulated SDCs. The LNFPIII‐activated SDCs had altered co‐stimulatory molecule expression compared with LPS‐stimulated SDCs, while the levels of SDC chemokines following activation by either compound were similar. LNFPIII‐activated SDCs produced significantly lower levels of interleukin‐12 but surprisingly higher levels of interleukin‐6 than LPS‐activated SDCs. Similar to previous studies using bone‐marrow‐derived DCs, LNFPIII‐activated SDCs induced strong Th2 responsesin vivoandex vivo.LNFPIII activation of APCs was independent of the Toll‐interleukin‐1 receptor adaptor myeloid differentiating factor 88. Importantly, LNFPIII‐matured DCs induced CD8+memory and effector CTL responses similar to those driven by LPS‐matured DCs, including the frequency of interferon‐γ‐producing CD8+T cells and induction of CTL effectors. Treatment of APCs by the anti‐inflammatory glycan LNFPIII did not impair their ability to drive CD8+effector and memory cell‐mediated immunity.