RETINOIC ACID UP-REGULATES HUMAN LANGERHANS CELL ANTIGEN PRESENTATION AND SURFACE EXPRESSION OF HLA-DR AND CD11C, A BETA-2 INTEGRIN CRITICALLY INVOLVED IN T-CELL ACTIVATION
RETINOIC ACID UP-REGULATES HUMAN LANGERHANS CELL ANTIGEN PRESENTATION AND SURFACE EXPRESSION OF HLA-DR AND CD11C, A BETA-2 INTEGRIN CRITICALLY INVOLVED IN T-CELL ACTIVATION
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DOI：
10.1111/1523-1747.ep12413014
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发表时间：
1994-12-01
影响因子：
6.5
通讯作者：
COOPER, KD
中科院分区：
文献类型：
--
作者：
MEUNIER, L;BOHJANEN, K;COOPER, KD
类维生素A的免疫调节作用可能是其抗癌和抗炎特性的一部分。研究了维甲酸（RA）对人表皮朗格汉斯细胞抗原提呈活性和角质形成细胞辅助细胞活性的影响。每名志愿者的两个皮肤部位分别用0.1% RA或溶剂进行体内处理，每天一次，持续4 d。RA处理的表皮细胞（RA-EC）同种异体抗原呈递给CD 4（+）T细胞在每个志愿者测试一致大于诱导的车辆EC。然而，这种抗原提呈活性的增加并不导致自身反应性CD 4（+）T淋巴细胞增殖。RA-EC的未分级表皮抗原呈递活性升高不是由于角质形成细胞主要组织相容性复合物（MHC）或细胞间粘附分子表达增加或其他角质形成细胞辅助信号传导，因为CD 1a（-）荧光激活细胞分选仪（FACS）纯化的RA-EC孵育抑制同种异体抗原呈递，推测是通过增加角质形成细胞转化生长因子-β。相比之下，朗格汉斯细胞功能上调;与来自载体EC的朗格汉斯细胞相比，来自RA-EC的FACS纯化的CD 1a（+）朗格汉斯细胞显示出显著增加的向T细胞呈递同种异体抗原的能力。三色流式细胞术分析RA-EC和载体EC悬浮液显示，RA处理没有改变DR（+）和CD 1a（+）DR（+）EC的数量，但确实导致朗格汉斯细胞HLA-DR、CD 11 c和CD 1c表达的统计学显著增加。另一个新的发现是HLA-DR依赖的朗格汉斯细胞在正常和RA处理的皮肤中的抗原提呈活性被抗CD 11 c抗体完全阻断。因此，类维生素A上调抗原呈递活性可能是由于上调朗格汉斯细胞CD 11 c，以及II类MHC。在没有自身反应性的人皮肤中皮肤免疫应答的上调以前没有报道过（据我们所知），并且所实现的朗格汉斯细胞表型和功能状态不同于以前报道的朗格汉斯细胞活化状态。
Immunomodulatory effects of retinoids may be part of their anti-carcinogenic and anti-inflammatory properties. We studied the in vivo effects of retinoic acid (RA) on antigen-presenting activity of human epidermal Langerhans cells and on accessory cell activity of keratinocytes. Two skin sites from each volunteer were treated in vivo with 0.1% RA or vehicle, respectively, once a day for 4 d. RA-treated epidermal cell (RA-EC) alloantigen presentation to CD4(+) T cells in each volunteer tested was consistently greater than that induced by vehicle EC. However, this increased antigen-presenting activity did not lead to autoreactive CD4(+) T-lymphocyte proliferation. Elevated unfractionated epidermal antigen-presenting activity of RA-EC was not due to increased keratinocyte major histocompatibility complex (MHC) or intercellular adhesion molecule expression or to other keratinocyte accessory signaling, because incubation of CD1a(-) flouroscence-activated cell sorter (FACS)-purified RA-EC inhibited alloantigen presentation, presumably through increased keratinocyte transforming growth factor-beta. By contrast, Langerhans cell function was upregulated; FACS-purified CD1a(+) Langerhans cells derived from RA-EC displayed a markedly increased ability, relative to Langerhans cells from vehicle EC, to present alloantigen to T cells. Triple color flow-cytometric analysis of RA-EC and vehicle EC suspensions revealed that RA treatment did not modify the number of DR(+) and CD1a(+)DR(+)EC, but did result in statistically significant increases in Langerhans cells expression of HLA-DR, CD11c, and CD1c. Another novel finding was that HLA-DR-dependent Langerhans cells antigen-presenting activity in both normal and RA-treated skin was completely blocked by anti-CD11c antibody. Thus, retinoid upregulation of antigen-presenting activity may be due to upregulation of Langerhans cell CD11c, as well as class II MHC. Up-regulation of cutaneous immune responsiveness in human skin without autoreactivity has not (to our knowledge) been reported previously, and the Langerhans cell phenotypic and functional state achieved is distinct from previously reported states of langerhans cell activation.