REGENERATIVE CAPACITY OF THE CD4+ T CELLS IN AIDS

描述(改编自调查人员的摘要)：这一目标 项目是了解再生和免疫生物学 HIV-1感染者外周血中CD_4~+T细胞功能的研究 它们对免疫恢复的影响。鉴于HIV-1感染的肆虐 关于CD4阳性的T细胞，研究人员假设再生的 随着疾病的发展，能力和曲目将逐渐减少。 或者，如果CD4阳性T细胞有取之不尽的能力 再生时，可以保持扩展容量和曲目。 区分这些可能性对以下方面有很大的影响 当有效的抗逆转录病毒治疗时免疫恢复的程度 已经成立了。在目前的项目中，第一个具体目标包括 测定CD4阳性T细胞扩增能力的实验设计 来自HIV-1感染不同阶段患者的细胞。主题是 再分为高病毒载量组和低病毒载量组。再生性 能力将与CD4+T细胞的再生能力进行比较 来自未感染的受试者和受感染的、长期无进展的人。在 第二个目标是，实验将检查免疫生物学谱系和 CD4+T细胞在重复有丝分裂过程中的功能 组织。全细胞免疫生物学功能的保存 分歧对免疫恢复的程度和持续时间都是个好兆头。 病毒复制停止后。在第三个具体目标中，选定了一个 将对CD4T细胞计数非常低的受试者亚组进行检查 测定治疗前后的再生能力和免疫生物学能力 他们已经接受了有效的抗逆转录病毒治疗。这些研究将是 纵向评估。这将提供证据，证明是否停止 病毒感染的破坏将允许高病毒感染的细胞逐渐返回 再生能力，如果新的CD4阳性T细胞 胸腺衍生而来。在具体目标四中，本研究的临床意义。 再生能力将被确定。

DESCRIPTION (adapted from the investigator's abstract): The goal of this project is to gain understanding of the regeneration and immunobiologic capacities of the CD4+ T cells in HIV-1 infected subjects, and to explore their implication for immune recovery. Given the ravages of HIV-1 infection on CD4 positive T cells, the investigator hypothesized that the regenerative capacity and repertoire will progressively diminish as the disease advances. Alternatively, if CD4 positive T cells have an inexhaustible ability to regenerate, the expansion capacity and repertoire may be maintained. Distinguishing between these possibilities have a strong implication as to the extent of immunologic recovery when effective anti-retroviral therapy is instituted. In the current project, the first specific aims include experiments designed to determine the expansion capacity of CD4 positive T cells from patients at various stages of HIV-1 infection. Subjects are sub-divided into groups with high and low viral loads. The regenerative capacity will be compared with the regenerative capacity of CD4+ T cells from uninfected subjects and infected, long term non-progressors. In the second aim, experiments will examine the immunobiological repertoire and function of CD4+ T cells as they advance through repetitive mitotic divisions. Preservation of the immunobiologic function through all cell divisions bode well for both the extent and duration of immunologic recovery after virus replication is halted. In the third specific aim, a selected sub-groups of subjects with very low CD4 T cell counts will be examined to determine the regenerative and immunobiologic capacities before and after they have received potent anti-retroviral therapy. These studies will be assessed longitudinally. This will provide evidence as to whether stopping the ravages of viral infection will permit gradual return of cells with high regenerative capacity as might be expected if new CD4 positive T cells are thymic derived. In specific aim four, the clinical significance of the regenerative capacity will be determined.