Kaminski M J, Cruz P D, Bergstresser P R, Takashima A
Department of Dermatology, University of Texas Southwestern Medical Center, Dallas 75235.
Cancer Res. 1993 Sep 1;53(17):4014-9.
Dendritic epidermal T-cells (DETC) are a unique population of T-cells that reside normally in mouse epidermis and express a gamma delta T-cell receptor. We have reported previously that DETC acquire in culture the capacity to lyse the YAC-1 lymphoma, a conventional target for natural killer cells. The aim of the present study was to characterize this cytotoxic potential, using a spectrum of skin-derived mouse tumors. Cytotoxicity was measured by a 51Cr release assay and by the visual assessment of target cell lysis. Long-term DETC lines, established from CBA, AKR, and BALB/c mice by mitogenic stimulation and repeated feeding with interleukin 2 (5 units/ml), were used as effectors. Skin-derived tumor targets included 5 melanoma lines and the transformed keratinocyte line Pam 212. Each DETC line lysed skin-derived tumors as well as YAC-1 targets effectively in the 18-h 51Cr release assay, and target lysis occurred in a non-major histocompatibility complex-restricted manner. By contrast, freshly isolated spleen cells lysed YAC-1 but not skin tumor targets. Moreover, confluent monolayers of melanoma or Pam 212 targets were disrupted completely by added DETC lines but not by spleen cells. The cytolytic activity of DETC appeared to be specific for tumor cells, since normal mouse keratinocyte monolayers remained intact under the same conditions. Finally, DETC freshly isolated from skin failed to exhibit significant cytotoxicity but acquired this capacity 10-14 days after mitogenic stimulation and feeding with interleukin 2 (5 units/ml). We conclude that DETC possess the potential to recognize, bind, and lyse tumor cells that originate in skin.
树突状表皮T细胞(DETC)是一类独特的T细胞群体,通常存在于小鼠表皮中,并表达γδ T细胞受体。我们之前报道过,DETC在培养过程中获得了裂解YAC-1淋巴瘤的能力,YAC-1淋巴瘤是自然杀伤细胞的传统靶标。本研究的目的是利用一系列源自皮肤的小鼠肿瘤来表征这种细胞毒性潜力。细胞毒性通过51Cr释放试验和对靶细胞裂解的视觉评估来测量。通过丝裂原刺激并用白细胞介素2(5单位/毫升)反复培养,从CBA、AKR和BALB/c小鼠建立的长期DETC系用作效应细胞。源自皮肤的肿瘤靶标包括5种黑色素瘤系和转化的角质形成细胞系Pam 212。在18小时的51Cr释放试验中,每个DETC系均能有效裂解源自皮肤的肿瘤以及YAC-1靶标,并且靶标裂解以非主要组织相容性复合体限制的方式发生。相比之下,新鲜分离的脾细胞能裂解YAC-1,但不能裂解皮肤肿瘤靶标。此外,添加的DETC系可完全破坏黑色素瘤或Pam 212靶标的汇合单层细胞,但脾细胞则不能。DETC的细胞溶解活性似乎对肿瘤细胞具有特异性,因为在相同条件下正常小鼠角质形成细胞单层保持完整。最后,从皮肤新鲜分离的DETC未表现出明显的细胞毒性,但在丝裂原刺激并用白细胞介素2(5单位/毫升)培养10 - 14天后获得了这种能力。我们得出结论,DETC具有识别、结合和裂解源自皮肤的肿瘤细胞的潜力。