Converse P J, Fehniger T E, Ehrnst A, Strannegård O, Britton S
Department of Infectious Diseases, Roslagstull Hospital, Karolinska Institute, Stockholm, Sweden.
Clin Exp Immunol. 1990 Dec;82(3):559-66. doi: 10.1111/j.1365-2249.1990.tb05490.x.
In order to delineate the molecular pathogenesis of the increased susceptibility to CMV disease in HIV infection, the patterns of antigen responsiveness in HIV-infected and non-infected individuals were investigated. CMV was fractionated by SDS-PAGE and electroblotted onto nitrocellulose. Lymphoproliferative responses of healthy HIV-, CMV+ individuals and HIV+, CMV+ asymptomatic patients to a whole CMV antigen preparation and to 20 fractions of nitrocellulose-bound CMV were then compared. Three fractions of approximate molecular weight of 130-165, 65-75, and 55-65 kD appeared to contain the major T cell stimulating antigens for HIV-, CMV+ individuals. A statistically significant depression of responses to fractions containing antigens in the ranges of 130-165 kD and 55-65 kD but not to whole CMV was seen in HIV+ individuals compared with controls. In healthy controls, the sum of the proliferative responses as measured by 3H-thymidine uptake to these three major fractions was approximately equal to the response to a whole CMV antigen preparation, whereas it was less than half of this response in five out of six HIV+ subjects. When antibody activities to CMV antigens were analysed by immunoblotting of sera from the two subject groups and also sera of ARC and AIDS patients, a selective loss of reactivity was revealed in 10 out of 19 HIV+ subjects to a band of 26-28 kD whereas all 15 HIV-, CMV+ controls recognized this band. Serum IgG and IgM values were both significantly higher in HIV+ individuals than in controls. These findings suggest that specific lesions in the repertoire of immune responsiveness to CMV antigens occur in HIV+ individuals.
为了阐明HIV感染中巨细胞病毒(CMV)疾病易感性增加的分子发病机制,研究了HIV感染个体和未感染个体的抗原反应模式。通过SDS-PAGE对CMV进行分级分离,并电转印到硝酸纤维素膜上。然后比较了健康的HIV阴性、CMV阳性个体以及HIV阳性、CMV无症状患者对完整CMV抗原制剂和20个硝酸纤维素结合的CMV分级部分的淋巴细胞增殖反应。分子量约为130 - 165、65 - 75和55 - 65 kD的三个分级部分似乎含有HIV阴性、CMV阳性个体的主要T细胞刺激抗原。与对照组相比,HIV阳性个体对分子量在130 - 165 kD和55 - 65 kD范围内含抗原的分级部分的反应有统计学意义的降低,但对完整CMV的反应无降低。在健康对照组中,通过³H-胸腺嘧啶核苷摄取测量的对这三个主要分级部分的增殖反应总和大致等于对完整CMV抗原制剂的反应,而在六名HIV阳性受试者中有五名该反应小于此反应的一半。当通过对两组受试者以及ARC和AIDS患者血清进行免疫印迹分析CMV抗原的抗体活性时,发现19名HIV阳性受试者中有10名对26 - 28 kD条带的反应性选择性丧失,而所有15名HIV阴性、CMV阳性对照组均识别该条带。HIV阳性个体的血清IgG和IgM值均显著高于对照组。这些发现表明,HIV阳性个体在对CMV抗原的免疫反应库中存在特异性损伤。