Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden.
AIDS. 2013 Apr 24;27(7):1071-80. doi: 10.1097/QAD.0b013e32835ecaca.
To study whether in-vivo recruitment of dendritic cells in response to antigen administration in the skin is altered during HIV-1 infection.
Skin punch biopsies were collected from HIV-1-positive as well as seronegative individuals at 48 h after intradermal injection of inactivated antigens of mumps virus, Candida albicans, or purified protein derivate (PPD) from Mycobacterium tuberculosis.
Cryosections were analyzed by in-situ staining and computerized imaging.
Control skin biopsies showed that there was no difference in the number of skin-resident dendritic cells between seronegative and HIV-1-positive individuals. Antigen injection resulted in substantial infiltration of dendritic cells compared to the frequencies found in donor-matched control skin. In HIV-1-positive individuals, CD123(+)/CD303(+) plasmacytoid dendritic cells and CD11c myeloid dendritic cells, including the CD141(+) cross-presenting subset, were recruited at lower levels compared to healthy controls in response to PPD and mumps but not C. albicans. The level of dendritic cell recruitment correlated with the frequencies of T cells infiltrating the respective antigen sites. Ki67(+) cycling T cells at the injection sites were much more frequent in response to each of the antigens in the HIV-1-positive individuals, including those with AIDS, compared to healthy controls.
Multiple dendritic cell subsets infiltrate the dermis in response to antigen exposure. There was no obvious depletion or deficiency in mobilization of dendritic cells in response to antigen skin tests during chronic HIV-1 infection. Instead, the levels of antigen-specific memory T cells that accumulate at the antigen site may determine the level of dendritic cell infiltration.
研究 HIV-1 感染期间,皮肤内抗原递呈细胞(树突状细胞)的募集是否发生改变。
在 HIV-1 阳性和阴性个体中,于皮内注射腮腺炎病毒、白色念珠菌或结核分枝杆菌的纯化蛋白衍生物(PPD)48 小时后,采集皮肤活检标本。
对冷冻切片进行原位染色和计算机成像分析。
在阴性对照皮肤中,树突状细胞的数量在 HIV-1 阳性个体和阴性个体之间没有差异。与供体匹配的对照皮肤相比,抗原注射导致树突状细胞大量浸润。与健康对照组相比,HIV-1 阳性个体中,对 PPD 和腮腺炎病毒的反应,CD123(+) / CD303(+)浆细胞样树突状细胞和 CD11c 髓系树突状细胞(包括 CD141(+)交叉呈递亚群)的募集水平较低,但对白色念珠菌无此现象。树突状细胞的募集水平与浸润相应抗原部位的 T 细胞频率相关。与健康对照组相比,HIV-1 阳性个体中,Ki67(+)增殖 T 细胞在每个抗原部位的反应频率更高,包括 AIDS 患者。
多种树突状细胞亚群在抗原暴露时浸润真皮。在慢性 HIV-1 感染期间,针对抗原皮肤试验,树突状细胞的动员并没有明显耗竭或缺乏。相反,在抗原部位积累的抗原特异性记忆 T 细胞的水平可能决定了树突状细胞的浸润程度。