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，并取得了如下成果。Uchiyama报告说，天然α干扰素产生细胞是某些树突状细胞亚群的前体，在先天免疫反应中起着至关重要的作用，可能被HIV-1感染并产生大量α干扰素以响应HIV-1感染分化为树突状细胞。Nagasawa发现了最不成熟的前体B细胞的一个亚群，并通过各种敲除小鼠表明，SDF-1对该细胞亚群的发育至关重要。Yoshie分析了免疫趋化因子组成性表达在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，用gp160-fusogenic lipo质体经鼻黏膜免疫，不仅在野生型小鼠中，而且在IFN-γ敲除小鼠或il -4敲除小鼠中均可诱导中和抗体应答，这表明该疫苗可能具有治疗性。Takahashi详细报道了CTL对HIV-1感染的反应机制。Takizawa发现hiv -1特异性CD8(+) CTL在其表面表达CCR5并通过该配体迁移，表明这些化学因子可能参与了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.