Romani N, Koide S, Crowley M, Witmer-Pack M, Livingstone A M, Fathman C G, Inaba K, Steinman R M
Rockefeller University, New York, New York 10021.
J Exp Med. 1989 Mar 1;169(3):1169-78. doi: 10.1084/jem.169.3.1169.
The capacity of dendritic cells to present protein antigens has been studied with two MHC class II-restricted, myoglobin-specific, T cell clones. Spleen dendritic cells and cultured epidermal Langerhans cells (LC) presented native myoglobin weakly and often not at all. These same populations were powerful stimulators of allogeneic T cells in the primary MLR. Freshly isolated LC were in contrast very active in presenting proteins to T cell clones but were weak stimulators of the MLR. Both fresh and cultured LC could present specific peptide fragments of myoglobin to the clones. These results suggest that dendritic cells in nonlymphoid tissues like skin can act as sentinels for presenting antigens in situ, their accessory function developing in two phases. First antigens are captured and appropriately presented. Further handling of antigen then is downregulated while the cells acquire strong sensitizing activity for the growth and function of resting T lymphocytes. The potent MLR stimulating activity of cultured epidermal LC and lymphoid dendritic cells probably reflects prior handling of antigens leading to the formation of allogeneic MHC-peptide complexes.
利用两个MHC II类分子限制的、肌红蛋白特异性的T细胞克隆,对树突状细胞呈递蛋白质抗原的能力进行了研究。脾树突状细胞和培养的表皮朗格汉斯细胞(LC)呈递天然肌红蛋白的能力较弱,且常常根本无法呈递。在初次混合淋巴细胞反应(MLR)中,这些细胞群体却是同种异体T细胞的强大刺激剂。相比之下,新鲜分离的LC在向T细胞克隆呈递蛋白质方面非常活跃,但对MLR的刺激作用较弱。新鲜的和培养的LC都能将肌红蛋白的特异性肽片段呈递给克隆。这些结果表明,皮肤等非淋巴组织中的树突状细胞可作为原位呈递抗原的哨兵,其辅助功能分两个阶段发展。首先捕获抗原并进行适当呈递。随后,抗原的进一步处理被下调,而细胞则获得对静息T淋巴细胞的生长和功能的强大致敏活性。培养的表皮LC和淋巴树突状细胞强大的MLR刺激活性可能反映了之前对抗原的处理导致了同种异体MHC-肽复合物的形成。