DENDRITIC CELL THERAPY FOR HIV--ROLE OF CYTOKINES ON ENHANCED T CELL FUNCTION

高效抗逆转录病毒药物治疗HIV感染者 治疗(HAART)方案显著降低了HIV-1病毒载量 以及外周血中CD4+T细胞计数的改善。然而，还有 仅靠HAART可能不会导致完全恢复正常的证据 淋巴细胞的数量和功能，特别是艾滋病毒特异性免疫 功能。我们假设用自体免疫进行治疗性免疫 培养的DC，适当负载HIV抗原，将导致 在小鼠体内产生对HIV-1更有效的细胞免疫应答 设置有效的抗逆转录病毒治疗。我们建议调查 接受HAART的HIV感染患者来源的DC有可能 激发强协同(CTL和Th)HIV特异性的潜力 体外细胞反应。这个体外模型将使我们能够确定 树突状细胞构建HIV特异性免疫的可行性研究 在有效的抗逆转录病毒治疗后给药。在目标1中，我们 会将HIV抗原传递给自体培养的DC，以刺激 并维持HIV特异性T细胞反应。在目标2中，我们将评估 已知可促进细胞免疫的细胞因子对血管内皮细胞 产生的抗原特异性T细胞反应的大小和多样性 在体外使用抗原致敏的DC。在目标3中，我们将调查 DC-T细胞相互作用对HIV-1体外复制的影响 在这种情况下，细胞因子在调节艾滋病毒复制中所起的作用。在……里面 目的4我们将执行临床方案，以评估安全性和 负载HIV的自体培养树突状细胞的免疫原性和Recall 抗原，以及在随后的结合细胞因子的试验中， 用于接受HAART的艾滋病毒感染患者。

Treatment of HIV-infected patients with highly active anti-retroviral therapy (HAART) regimens has led to marked reductions in HIV-1 viral load and improvements in peripheral CD4+ T cell counts. However, there is evidence that HAART alone may not result in complete return of normal lymphocyte number and function, and, in particular, HIV-specific immune function. We hypothesize that therapeutic immunization with autologous cultured DC, appropriately loaded with HIV antigens, will lead to the generation of a more effective cellular immune response to HIV-1 in the setting of effective anti-retroviral therapy. We propose to investigate the possibility that DC derived from HIV-infected patients on HAART have the potential to stimulate a strong, coordinate (CTL and Th) HIV-specific cellular response in vitro. This in vitro model will allow us to determine the feasibility of reconstituting HIV-specific immunity using DC administration following effective anti-retroviral therapy. In Aim 1 we will deliver HIV antigens to autologous cultured DC in order to stimulate and maintain HIV-specific T cell responses. In Aim 2 we will evaluate the impact of cytokines known to promote cell-mediated immunity on the magnitude and diversity of the antigen-specific T cell responses generated in vitro using antigen-primed DC. In Aim 3, we will investigate the effects of DC-T cell interactions on HIV-1 replication in vitro, and the role that cytokines play in regulating HIV replication in this setting. In Aim 4 we will perform clinical protocols to evaluate the safety and immunogenicity of autologous cultured DC, loaded with HIV and recall antigens, and in subsequent trials in combination with cytokines, administered to HIV-infect patients receiving HAART.