AIDS, SUPERANTIGENS, AND T-CELL RECEPTOR GENES

人类感染HIV的最终后遗症是CD 4 T细胞的丧失， 免疫系统受损，对机会性感染易感性， 不寻常的肿瘤和最终的死亡。 虽然直接的细胞病变 HIV对CD 4细胞的影响在艾滋病中无疑是重要的 发病机制，这些影响似乎并不能完全解释严重的 与疾病相关的免疫缺陷。 具有超抗原性的细菌、支原体和病毒的产物 特性几乎完全基于 VBeta的表达。 T淋巴细胞与超抗原的结合导致 不能扩增并最终导致接合细胞凋亡。 HIV或其他次级微生物病原体的超抗原可能 直接或间接导致艾滋病典型的CD 4损失， 间接促进病毒的传染性和复制。 最近 数据表明，艾滋病与特定的V β缺失有关， 克隆，HIV表现出某些VBeta克隆类型的优先感染性 艾滋病患者的T细胞容易凋亡， 超抗原性的表现。 本报告提出的研究将 确定V β克隆变化是否是艾滋病的特征， 通过检测V β， 来自所有疾病组的HIV感染患者中的所有疾病，包括 单卵双胞胎不一致和一致的这种疾病。 此外，委员会认为， HIV可能的超抗原活性将在体外进行评估， 在HIV感染的同基因培养物中检测V β刺激， 对恶性、VBeta转染或细菌的感染性 表达特异性VBetas的超抗原刺激的T细胞及其作用 HIV对胸腺器官培养中发育中的人类免疫系统的影响。 HIV重组蛋白特异性T细胞中的V β基因 克隆也将被确定。 体内诱导的HIV克隆丢失， 相关蛋白质也将在SCID小鼠-人胎儿中进行评估。 胸腺/肝脏模型。 综合研究将提供重要线索 艾滋病相关免疫缺陷的发病机制，并将有 对预后、随访和治疗有重要意义， 以及该流行病的病原学基础。

The ultimate sequelae of HIV infection in humans are loss of CD4 T cells, immune system compromise, susceptibility to opportunistic infections and unusual neoplasms, and eventual death. Although the direct cytopathic effects of HIV on CD4 cells are undoubtedly important in AIDS pathogenesis, these effects do not appear to fully account for the severe immunodeficiencies associated with the disease. Products of bacteria, mycoplasmas and viruses with superantigenic properties engage large sets of T cell clones almost solely on the basis of VBeta expression. T lymphocyte engagement by superantigens leads to anergy of expansion and eventual apoptotic death of the engaged cells. Superantigens of HIV or other secondary microbial pathogens may contribute to the CD4 loss that typifies AIDS either directly or indirectly by promoting infectivity and replication of the virus. Recent data suggest that AIDS is associated with deletion of specific VBeta clone, HIV exhibits preferential infectivity of certain VBeta clone types and T cells from AIDS patients are prone to apoptosis, all possible manifestations of superantigenicity. The studies proposed herein will determine whether VBeta clonal changes are characteristic of AIDS and are involved in the pathogenesis of this disease by examining VBeta repertoires in HIV-infected patients from all disease groups, including monozygotic twins discordant and concordant for this disease. Moreover, possible superantigenic activities of HIV will be assessed in vitro by examining VBeta stimulation in HIV-infected syngeneic cultures, degree of infectivity for malignant, VBeta transfected or bacterial superantigen-stimulated T cells expressing specific VBetas, and effects of HIV on the developing human immune system in thymic organ cultures. The VBeta genes represented in HIV recombinant protein-specific T cell clones will also be ascertained. In vivo induced clonal loss of HIV and related proteins will also be evaluated in the SCID mouse-human fetal thymus/liver model. The combined studies will provide important clues to the pathogenesis of AIDS-associated immunodeficiency, and will have significant implications for the prognosis, follow-up and treatment as well as etiologic basis of this epidemic disease.