Basic Research for AIDS control A02 ; Pathophysiology and immunology of HIV-1 infection

我们主要对HIV-1感染中的趋化因子/趋化因子受体系统和HIV-1特异性CTL进行了研究，取得了许多成果，如下所述。Uchiyama报道说，天然的α干扰素产生细胞是某些树突状细胞亚群的前体，在先天免疫反应中发挥关键作用，它可以感染HIV-1，并在感染HIV-1时产生大量的α干扰素，以分化为树突状细胞。长泽鉴定了最不成熟的前体B细胞的一个子集，并表明SDF-1对于使用各种基因敲除小鼠发展这个细胞亚群是必不可少的。Yoshie分析了淋巴器官中结构性表达的免疫趋化因子在HIV-1感染中的作用。他还分析了P2G-SDF-1-Fc嵌合蛋白对HIV-1感染的抑制作用。Kiyono报道，gp160融合脂质体经鼻粘膜免疫不仅在野生型小鼠中诱导了中和抗体应答，而且在干扰素-γ基因敲除小鼠或IL-4基因敲除小鼠中也诱导了中和抗体应答，提示该疫苗可能作为治疗性疫苗。Takahashi报道了CTL对HIV-1感染的详细反应机制。Takizawa发现，HIV-1特异性CD8()CTL在其表面表达CCR5，并被该配体迁移，表明这些趋化因子可能参与了Th1反应的诱导。

We have been worked mainly on chemokine/chemokine receptor system in HIV-1 infection and HIV-1-specific CTL, and got many results as described below. Uchiyama reported that natural alpha interferon-producing cells, which was a precursor of certain dendritic cell subsets and played a crucial role in an innate immune response, could be infected with HIV-1 and produce a large amount of alpha interferon in response to HIV-1 infection to differentiate into dendritic cells. Nagasawa identified a subset of the most immature precursor B cells and showed that SDF-1 is essential for the development of this cell subset using various knockout mice. Yoshie analyzed the role of immune chemokine constitutively expressed in lymphoid organs in HIV-1 infection. He also analyzed the suppressive effect of P2G-SDF-1-Fc chimeric protein on HIV-1 infection. Kiyono reported that immunization with gp160-fusogenic liposome through nasal mucosa induced the neutralizing antibodies response in not only wild type mice but also IFN-γ-knockout mice or IL-4-knockout mice, indicating a possible implication of this vaccine as a therapeutic vaccine. Takahashi reported detailed mechanism of CTL response to HIV-1 infection. Takizawa found that HIV-1-specific CD8(+) CTL expressed CCR5 on their surfaces and migrated by this ligand, indicating that these chemikines might be involved in the induction of Th1 response.