Alcalay J, Kripke M L
Department of Immunology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
J Immunol. 1991 Mar 15;146(6):1717-21.
The induction of skin cancers in mice by chronic UV irradiation is accompanied by a decrease in the numbers of Ia+ and Thy-1+ dendritic cells in the epidermis early in the course of UV irradiation. Subsequently, the number of Ia+ cells, but not Thy-1+ cells, increases until the time of tumor development. To assess the functional significance of these changes in cutaneous immune cells, and to help define the role these cells may play in immune surveillance against skin cancers, we tested the afferent immunologic capability of the skin during the development of UV-B radiation-induced skin cancers. Afferent immune function was measured by testing the Ag-presenting capacity of draining lymph node (DLN) cells from mice sensitized epicutaneously with dinitrofluorobenzene. A reduced contact hypersensitivity response was induced in mice immunized with DLN cells from UV-irradiated mice that had been sensitized with hapten on UV-irradiated skin. This decreased reactivity was present during the entire latent period of tumor development. However, in tumor-bearing mice, the DLN cells from UV-irradiated, sensitized animals exhibited normal Ag-presenting activity. DLN cells from UV-irradiated mice sensitized on ventral, unirradiated skin exhibited normal Ag-presenting activity. The lowest amount of Ag-presenting activity in the draining lymph nodes of UV-irradiated mice correlated temporally with the lowest number of Ia+, adenosine triphosphatase+ dendritic epidermal cells in the UV-irradiated skin. At least during the early part of the tumor latent period, an increase in the number of these cells was paralleled by an increase in the Ag-presenting activity of the DLN cells. In contrast, the number of Thy-1+ dendritic epidermal cells in UV-irradiated skin did not correlate with the Ag-presenting activity. Thus, the decrease in the number of identifiable epidermal Langerhans cells early in the course of chronic UV irradiation correlated with a decrease in Ag-presenting activity after sensitization through the UV-irradiated skin. These studies demonstrate that the afferent arm of the cutaneous immune response is impaired in the site of tumor development throughout the latent period of UV carcinogenesis.
慢性紫外线照射诱导小鼠皮肤癌的过程中，在紫外线照射早期，表皮中Ia +和Thy - 1 +树突状细胞数量会减少。随后，在肿瘤发生前，Ia +细胞数量会增加，但Thy - 1 +细胞数量不会增加。为了评估皮肤免疫细胞这些变化的功能意义，并帮助确定这些细胞在皮肤癌免疫监视中可能发挥的作用，我们在紫外线B辐射诱导的皮肤癌发生过程中测试了皮肤的传入免疫能力。通过检测经二硝基氟苯表皮致敏的小鼠引流淋巴结（DLN）细胞的抗原呈递能力来测量传入免疫功能。在用半抗原致敏过的紫外线照射小鼠的DLN细胞免疫的小鼠中，诱导出了降低的接触性超敏反应。这种反应性降低在肿瘤发生的整个潜伏期都存在。然而，在荷瘤小鼠中，来自紫外线照射、致敏动物的DLN细胞表现出正常的抗原呈递活性。在未照射的腹部皮肤致敏的紫外线照射小鼠的DLN细胞表现出正常的抗原呈递活性。紫外线照射小鼠引流淋巴结中最低量的抗原呈递活性在时间上与紫外线照射皮肤中Ia +、三磷酸腺苷酶 +树突状表皮细胞的最低数量相关。至少在肿瘤潜伏期的早期，这些细胞数量的增加与DLN细胞抗原呈递活性的增加平行。相比之下，紫外线照射皮肤中Thy - 1 +树突状表皮细胞的数量与抗原呈递活性无关。因此，在慢性紫外线照射早期，可识别的表皮朗格汉斯细胞数量的减少与通过紫外线照射皮肤致敏后抗原呈递活性的降低相关。这些研究表明，在紫外线致癌的整个潜伏期，皮肤免疫反应的传入臂在肿瘤发生部位受损。
