蕈样肉芽肿皮损中树突细胞和凋亡的研究

Apoptosis and Dendritic Cells in Skin Lesions of Mycosis Fungoides

目的探讨细胞凋亡与蕈样肉芽肿(MF)疾病进程和树突细胞(DC)的关系。方法皮肤肿瘤组织冰冻切片,单克隆抗体免疫组化多染及TdT介导的dUTP缺口末端标记技术(TUNEL)。结果MF斑片斑块期肿瘤组织Pautrier微脓肿内及真皮T细胞浸润区内可见少量凋亡细胞或凋亡小体,肿瘤期真皮T细胞浸润区内可见大量凋亡瘤细胞或凋亡小体(P<0.01)。部分肿瘤组织真皮深层凋亡细胞成片分布,这些区域常见许多未成熟的DC及包绕吞噬有凋亡瘤细胞或凋亡小体的未成熟的(Lag+,CD1a+)DC存在,斑片及斑块期不易见到这种现象。结论凋亡瘤细胞或凋亡小体的出现和增多可能是MF疾病进展的一个病理征象,肿瘤期中包绕吞噬凋亡瘤细胞或凋亡小体的未成熟的CD1a+DC出现提示在诱导抗肿瘤免疫方面存在交叉呈递,可能诱导抗肿瘤免疫耐受。

Objective To study apoptosis and dendritic cells (DC) in skin lesions of mycosis fungoides and their relation to the disease course. Methods Monoclonal antibody (mAb) and immunohistochemical multiple staining were used to detect the expression of special antigen on the surface of DC, which indicating an immature DC (iDC). Apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) test. Results In the lesions of patch/plaque-stage (PS) a few apoptotic cells were found in Pautrier′s microabscesses and in the dermal T cell infiltrated area, and large number of apoptotic tumor cells were observed in the dermal T cell infiltrated area of tumor stage (TS) (P < 0.01), especially densely interspersing in lower dermis. Immunohistochemical study showed that there were large amount of immature DC and apoptotic tumor cells phagocytized and surrounded by immature Lag+ and CD1a+ DC in the deep dermis. This phenomenon was rarely found in the lesions of plaque stage. Conclusions The appearance and increasing apoptosis in MF lesions may be an important pathological character of MF in progressive stage. The phenomenon of apoptotic tumor cells surrounded and phagocytized by iDC suggests the cross-presenting in inducing anti-tumor immunity, which may induce anti-tumor immunologic tolerance.