Imai Yasutomo, Hayashi Nobuki, Yasuda Koubun, Tsutsui Hiroko, Mizutani Hitoshi, Nakanishi Kenji
Department of Dermatology, Mie University School of Medicine, Tsu 514-8507, Japan.
J Dermatol Sci. 2008 Jul;51(1):19-29. doi: 10.1016/j.jdermsci.2008.01.005. Epub 2008 Mar 25.
Epidermal Langerhans cells (LCs) have been believed to function as professional antigen-presenting cells (APCs). However, LC-ablated mice reportedly suffer from severer contact hypersensitivity (CHS) upon cutaneous challenge with hapten than wild-type mice, suggesting LCs as regulators of adaptive immune responses in the skin.
This study was designed to address the possible regulatory roles of LCs in the balanced primary adaptive immune responses to protein antigens.
LCs were freshly isolated from skin of BALB/c mice (>95% positive for MHC class II). Naïve CD4+ T cells reactive to ovalbumin (OVA) were purified by FACS-sorting from lymph node cells of DO11.10 BALB/c mice, labeled with CSFE, and incubated with OVA peptide in the presence of splenic dendritic cells (DCs) and/or LCs. Cell division frequencies were determined by the degree of serially diluted expressions of CSFE in the individual CD4+ T cells.
Approximately 70% of them underwent cell division when naïve CD4+ T cells were activated by OVA presented by splenic DCs. In contrast, LCs only very modestly induced their cell division. Furthermore, LCs inhibited the cell division induced by splenic DCs, and this regulatory action was abolished by prevention of their contact to other cells, but not by the treatment with neutralizing antibodies against IL-10 or TGF-beta, well-established regulatory cytokines.
LCs negatively regulate the primary adaptive T cell response, presumably allowing well-controlled immune response in the skin.
表皮朗格汉斯细胞（LCs）一直被认为作为专职抗原呈递细胞（APCs）发挥作用。然而，据报道，与野生型小鼠相比，经半抗原皮肤激发后，LCs缺失的小鼠会出现更严重的接触性超敏反应（CHS），这表明LCs是皮肤中适应性免疫反应的调节因子。
本研究旨在探讨LCs在对蛋白质抗原的平衡原发性适应性免疫反应中可能的调节作用。
从BALB/c小鼠皮肤中新鲜分离LCs（MHC II类阳性率>95%）。通过荧光激活细胞分选（FACS）从DO11.10 BALB/c小鼠的淋巴结细胞中纯化对卵清蛋白（OVA）反应性的初始CD4+ T细胞，用羧基荧光素二乙酸琥珀酰亚胺酯（CSFE）标记，并在脾树突状细胞（DCs）和/或LCs存在的情况下与OVA肽一起孵育。通过单个CD4+ T细胞中CSFE连续稀释表达的程度来确定细胞分裂频率。
当脾DCs呈递的OVA激活初始CD4+ T细胞时，约70%的细胞发生分裂。相比之下，LCs仅非常适度地诱导其细胞分裂。此外，LCs抑制脾DCs诱导的细胞分裂，并且这种调节作用通过阻止它们与其他细胞接触而被消除，但用针对白细胞介素-10（IL-10）或转化生长因子-β（TGF-β）（公认的调节细胞因子）的中和抗体处理则不能消除。
LCs对原发性适应性T细胞反应起负调节作用，推测这使得皮肤中的免疫反应得到良好控制。
