Human dermal dendritic cells process and present soluble protein antigens
Human dermal dendritic cells process and present soluble protein antigens
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DOI：
10.1046/j.1523-1747.1998.00189.x
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发表时间：
1998-05-01
影响因子：
6.5
通讯作者：
Burg, G
中科院分区：
文献类型：
--
作者：
Nestle, FO;Filgueira, L;Burg, G
最近，在正常人和小鼠皮肤的真皮中发现了一种新型的树突状抗原提呈细胞。这些真皮树突状细胞(DDC)的数量高于表皮朗格汉斯细胞，代表了树突状细胞独特的分化途径，在激活超抗原特异性T细胞方面与朗格汉斯细胞一样强大。到目前为止，关于它们摄取、处理和呈递可溶性蛋白抗原的能力尚不清楚，我们使用破伤风环状病毒(TT)驱动的T细胞增殖模型来解决这些问题。为了检测TT蛋白的主动内化，金标记的TT与朗格汉斯细胞和DDC孵育，并可追踪到多囊泡内溶酶体室。DDC通过受体介导的、不依赖于笼蛋白的途径内化TT，而朗格汉斯细胞主要通过巨噬细胞吞噬作用来内化TT。为了证实DDC通过外源性抗原提呈途径处理TT，我们用TT蛋白或TT多肽冲击DDC，氯喹预孵育使DDC诱导TT蛋白特异性T细胞增殖的能力减弱(70-80%)，但不能有效抑制TT肽诱导的T细胞反应。DDC在向自身静息T细胞递呈TT方面的能力与朗格汉斯细胞相当，是塑料贴壁单核细胞的5-10倍，而且，仅有50个DDC(刺激物：反应比为1：1000)就能诱导显著的TT特异性T细胞增殖，因为DDC亚群表达低水平的CD1a，CD1a是朗格汉斯细胞的表型标志，对CD1a阳性和阴性的DDC进行了分选。在每个细胞的基础上，CD1a阳性和阴性的DDC在介导TT特异性T细胞增殖方面同样有效。因此，DDC能够内化、加工和呈递TT等可溶性蛋白抗原，因此可能在皮肤免疫反应的调节中发挥重要作用。
Recently, a novel type of dendritic antigen-presenting cell has been identified in the dermis of normal human and mouse skin. These dermal dendritic cells (DDC) occur in higher numbers than epidermal Langerhans cells, represent a distinct differentiation pathway of dendritic cells, and are as potent as Langerhans cells in the activation of superantigen specific T cells. As yet, nothing is known about their capacity to take up, process, and present soluble protein antigens, We used the model of tetanus toroid (TT) driven T cell proliferation to address these questions. To test for active internalization of TT protein, gold labeled TT was incubated with Langerhans cells and DDC and could be traced to multivesicular endo-lysosomal compartments. DDC internalize TT through a receptor-mediated, clathrin-independent pathway, whereas Langerhans cells predominantly use macropinocytosis., To verify that DDC process TT by the exogenous pathway of antigen presentation, we pulsed DDC with TT protein or TT peptide after preincubation with chloroquine, Preincubation with chloroquine diminished the capacity of DDC to induce TT protein specific T cell proliferation (70-80%), but was not effective to suppress TT peptide induced T cell responses. DDC were as potent as Langerhans cells and 5-10 X more potent than plastic adherent monocytes in the presentation of TT to autologous resting T cells, Furthermore, as few as 50 DDC (stimulator:responder ratio of 1:1000) were able to induce a significant TT specific T cell proliferation, Because a subpopulation of DDC expresses low levels of CD1a, a phenotypic marker of Langerhans cells, sorting of CD1a positive and negative DDC was performed. On a per cell basis, CD1a positive and negative DDC were equally potent at mediating TT specific T cell proliferation. Thus, DDC are able to internalize, process, and present soluble protein antigens such as TT and may therefore play an important role in the regulation of skin immune responses.