Nestle F O, Turka L A, Nickoloff B J
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
J Clin Invest. 1994 Jul;94(1):202-9. doi: 10.1172/JCI117308.
Local activation of T lymphocytes is regarded as an important immunological component of psoriatic skin lesions. Within psoriatic plaques (PP) there are large numbers of dermal dendritic cells (DDCs) immediately beneath the hyperplastic epidermis surrounded by T cells. In this study we investigated the ability of DDCs isolated from PP skin to support immune responses to resting peripheral blood T cells. For comparison, other dendritic cells were obtained from blood of the same psoriatic patients, as well as DDCs from skin of normal healthy individuals (designated NN skin). All dendritic cells studied had high surface expression of HLA-DR, B7, and lymphocyte function associated antigen-1 molecules. T cell proliferative responses and cytokine production profiles to these various dendritic cells were measured in the absence and presence of PHA or bacterial-derived superantigens. In the absence of exogenous mitogens, PP skin-derived DDCs were much more effective stimulators of spontaneous T cell proliferation compared with either psoriatic blood-derived or NN skin-derived dendritic cells. Antibody blocking studies revealed involvement of HLA-DR, B7, and lymphocyte function associated antigen-1 on PP skin-derived DDCs. Cytokine profiles revealed that in the absence of exogenous stimuli PP skin-derived DDCs mediated a T cell response with high levels of IL-2 and IFN-gamma, but not IL-4 or IL-10. NN skin-derived DDCs produced a similar qualitative response, but quantitative amounts of all cytokines measured were lower. Upon addition of PHA or superantigens, both PP skin-derived and NN skin-derived DDCs mediated high levels of IL-2 and IFN-gamma production, with induction of IL-4 particularly evident for PHA reactions. Addition of conditioned medium from psoriatic dermal fragments did not enhance the autostimulatory capacity of blood-derived dendritic cells. These findings highlight the potent autostimulatory potential of PP skin-derived DDCs and suggest an important immunological contribution for these previously overlooked cell types contained within lesional skin sites.
T淋巴细胞的局部激活被认为是银屑病皮肤病变重要的免疫组成部分。在银屑病斑块（PP）内，增生性表皮下方紧邻大量真皮树突状细胞（DDC），周围环绕着T细胞。在本研究中，我们调查了从PP皮肤分离的DDC支持对静息外周血T细胞免疫反应的能力。为作比较，还从相同银屑病患者的血液中获取了其他树突状细胞，以及来自正常健康个体皮肤的DDC（称为NN皮肤）。所有研究的树突状细胞均高表达HLA-DR、B7和淋巴细胞功能相关抗原-1分子。在有无PHA或细菌来源的超抗原存在的情况下，检测了对这些不同树突状细胞的T细胞增殖反应和细胞因子产生情况。在没有外源性有丝分裂原的情况下，与银屑病血液来源或NN皮肤来源的树突状细胞相比，PP皮肤来源的DDC是更有效的自发T细胞增殖刺激物。抗体阻断研究表明HLA-DR、B7和淋巴细胞功能相关抗原-1参与了PP皮肤来源的DDC作用。细胞因子谱显示，在没有外源性刺激的情况下，PP皮肤来源的DDC介导了高水平IL-2和IFN-γ的T细胞反应，但不产生IL-4或IL-10。NN皮肤来源的DDC产生了类似的定性反应，但所有检测细胞因子的定量水平较低。加入PHA或超抗原后，PP皮肤来源和NN皮肤来源的DDC均介导了高水平的IL-2和IFN-γ产生，PHA反应中IL-4的诱导尤为明显。添加银屑病真皮碎片的条件培养基并未增强血液来源树突状细胞的自刺激能力。这些发现突出了PP皮肤来源的DDC强大的自刺激潜力，并表明这些病变皮肤部位中以前被忽视的细胞类型具有重要的免疫作用。
