樹状細胞CD1分子による脂質抗原提示に対するHIV-1感染の影響

抄録

Dendritic cells (DCs) play an important role as professional antigen (Ag)-presenting cells in the context of HIV-1 infection and AIDS pathogenesis. DCs are unique, since all the CD1 molecules, namely CD1a, CD1b, CD1c and CD1d, are expressed in DCs. When DCs are infected with HIV-1, the product of HIV-1 accessory genes such as nef gene down-regulates both the lipid Ag presentation by CD1s and the peptide Ag presentation by MHC molecules, as well as their surface expression, which results in evasion from immune surveillance. It is also reported that CD1d-restricted NKT cells can be infected with HIV-1 and that their numbers are decreased in HIV-1 positive patients, which suggests the involvement of CD1 lipid Ag presentation in the context of HIV-1 infection. Thanks to anti-retroviral therapy (ART), the prognosis of patients with AIDS has been remarkably improved with the recovery of host immunity due to the suppression of HIV-1 proliferation. But HIV-1 survives ART in AIDS patients even after viral RNA levels become undetectable in the peripheral blood, hiding in so-called "reservoirs." Once ART is terminated, HIV-1 appears again. Therefore, we need to identify the HIV-1 reservoirs and exclude HIV-1 completely from them. DCs are strong candidates as HIV-1 reservoirs, so it is critical to clarify how HIV-1-infected DCs evade immune surveillance if AIDS is to be cured. In this review, we discuss the role of DCs in HIV-1 infection, and the role of hematopoietic cell kinase (Hck), which seems to be a key factor in the immune evasion of HIV-1 infected DCs. We also consider possible combination therapy with Hck inhibitors, lipid Ag stimulation of DCs and immune checkpoint inhibitors, in relation not only to AIDS but also to other chronic viral infections and malignant diseases.