Psoriatic skin-derived dendritic cell function is inhibited by exogenous IL-10. Differential modulation of B7-1 (CD80) and B7-2 (CD86) expression.
Psoriatic skin-derived dendritic cell function is inhibited by exogenous IL-10. Differential modulation of B7-1 (CD80) and B7-2 (CD86) expression.
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DOI：
10.4049/jimmunol.154.6.2668
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发表时间：
1995-03
影响因子：
4.4
通讯作者：
R. Mitra;T. Judge;F. Nestle;L. Turka;B. Nickoloff
中科院分区：
文献类型：
--
作者：
R. Mitra;T. Judge;F. Nestle;L. Turka;B. Nickoloff
免疫应答的调节依赖于APC和T细胞之间的相互作用。这种细胞相互作用由包括MHC II类Ag（DR）和CD 28配体B7-1（CD 80）和B7-2（CD 86）的表面分子介导。最近的证据表明，存在或不存在的共刺激分子的APC显着影响免疫应答的定性和定量性质。在这份报告中，我们分析了两个相关的细胞因子在皮肤免疫生物学，粒细胞-巨噬细胞（GM）-CSF和IL-10，并证明其对培养的树突状细胞从真皮（DDCs）的正常皮肤和银屑病病变。为了比较，将对这些专职APC的作用与培养的血液来源的单核细胞进行对比。正常和银屑病皮肤来源的DDC表达高水平的CD 86超过CD 80，并且总体层次是DR > CD 86> CD 80，而培养的单核细胞表达低水平和等同水平的CD 80和CD 86。如果在培养的初始阶段向GM-CSF中加入Ab，则迁移的DDC具有较低水平的CD 86，对CD 80或DR表达没有任何可检测的影响，并且显示出刺激超抗原驱动的或同种异体抗原应答性T细胞的能力降低。相反，通过向单核细胞中加入GM-CSF，CD 86水平提高。当在培养开始时加入IL-10时，DDC具有显著较低的CD 86水平，对CD 80或DR表达没有任何影响，并且与抗GM-CSF处理的细胞一样，这些DDC的T细胞刺激能力降低约50%。相比之下，当单核细胞用外源性添加的IL-10相同地处理时，它们保留其相对低水平的CD 80和CD 86，APC功能没有可检测的变化。阻断DDC：T细胞相互作用的研究表明，CD 86比CD 80更重要。因此，涉及这些APC群体的差异表达模式和功能性细胞因子应答可能与皮肤疾病如银屑病相关，其中存在CD 28配体表达的不一致模式和紊乱的细胞因子网络。
Regulation of immune responses depends on interactions between APCs and T cells. Such cellular interactions are mediated by surface molecules including MHC class II Ags (DR) and CD28 ligands B7-1 (CD80) and B7-2 (CD86). Recent evidence indicates that the presence or absence of costimulatory molecules on APCs significantly influences the qualitative and quantitative nature of an immune response. In this report, we analyze two relevant cytokines in skin immunobiology, granulocyte-macrophage (GM)-CSF and IL-10, and demonstrate their effects on cultured dendritic cells obtained from dermis (DDCs) of normal skin and psoriatic lesions. For comparison, the effects on these professional APCs were contrasted with cultured blood-derived monocytes. Normal and psoriatic skin-derived DDCs express high levels of CD86 over CD80, and the overall hierarchy is DR > CD86 > CD80, whereas cultured monocytes express low and equivalent levels of CD80 and CD86. If Ab is added to GM-CSF at the initial period of cultivation, DDCs that emigrate have lower levels of CD86 without any detectable effect on CD80 or DR expression and display a reduced capacity to stimulate either superantigen-driven or alloantigen-responsive T cells. Conversely, by adding GM-CSF to monocytes, CD86 levels are enhanced. When IL-10 was added at the beginning of culture, DDCs had significantly lower levels of CD86, without any effect on CD80 or DR expression, and like anti-GM-CSF-treated cells, these DDCs had approximately a 50% reduction in their T cell-stimulating capacity. In contrast, when monocytes were treated identically with exogenously added IL-10, they retained their relatively low levels of CD80 and CD86 with no detectable change in APC function. Blocking studies of DDC:T cell interaction indicated that CD86 was more important than CD80. Thus, differential expression patterns and functional cytokine responses involving these APC populations may be relevant to skin disorders such as psoriasis, in which discordant patterns of CD28 ligand expression and disordered cytokine networks are present.