Takamitsu Matsuzawa1, Youichi Ogawa2, Kohji Moriishi3, Shinji Shimada1, Tatsuyoshi Kawamura1. 1. Department of Dermatology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan. 2. Department of Dermatology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan. Electronic address: yogawa@yamanashi.ac.jp. 3. Department of Microbiology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan.
Abstract
BACKGROUND: Langerhans cells (LCs) are one of the initial target cells for HIV following sexual exposure and they are productively infected by HIV. HIV-infected LCs migrate to the draining lymph nodes (dLNs) and transmit the virus to CD4+ T cells, leading to the dissemination of HIV. In contrast with the role of LCs in initial HIV acquisition, little is known about the modulation of immune responses by HIV-infected LCs. OBJECTIVE: We aimed to elucidate the induction of HIV-specific CD8+ T cells and regulatory T cells (Tregs), both of which play important roles in regulating the progression of HIV infection. METHODS: We examined the inducibility of HLA-A*0201 restricted HIV-specific CD8+ T cells and Tregs by HIV-primed LCs or HIV-primed dendritic cells (DCs) as a control. RESULTS: The number of HIV-specific CD8+ T cells induced by HIV-primed monocyte-derived LCs (mLCs) was significantly higher than that by HIV-primed monocyte-derived DCs (mDCs). Additionally, HIV-specific CD8+ T cells induced by HIV-primed mLCs produced more IFN-γ than HIV-nonspecific CD8+ T cells. HIV-primed human epidermal LCs also induced IFN-γ-producing HIV-specific CD8+ T cells. As for the induction of Tregs, HIV-primed mLCs and human epidermal LCs significantly impaired the induction of FoxP3hiCD45RA- effector Tregs than HIV-unprimed mLCs and human epidermal LCs. CONCLUSIONS: HIV-primed LCs trigger beneficial immune responses against HIV infection through the increased induction of HIV-specific CD8+ T cells and the decreased induction of effector Tregs in the initial phase of HIV infection, thereby contributing to the prolonged onset of AIDS.
BACKGROUND: Langerhans cells (LCs) are one of the initial target cells for HIV following sexual exposure and they are productively infected by HIV. HIV-infected LCs migrate to the draining lymph nodes (dLNs) and transmit the virus to CD4+ T cells, leading to the dissemination of HIV. In contrast with the role of LCs in initial HIV acquisition, little is known about the modulation of immune responses by HIV-infected LCs. OBJECTIVE: We aimed to elucidate the induction of HIV-specific CD8+ T cells and regulatory T cells (Tregs), both of which play important roles in regulating the progression of HIV infection. METHODS: We examined the inducibility of HLA-A*0201 restricted HIV-specific CD8+ T cells and Tregs by HIV-primed LCs or HIV-primed dendritic cells (DCs) as a control. RESULTS: The number of HIV-specific CD8+ T cells induced by HIV-primed monocyte-derived LCs (mLCs) was significantly higher than that by HIV-primed monocyte-derived DCs (mDCs). Additionally, HIV-specific CD8+ T cells induced by HIV-primed mLCs produced more IFN-γ than HIV-nonspecific CD8+ T cells. HIV-primed human epidermal LCs also induced IFN-γ-producing HIV-specific CD8+ T cells. As for the induction of Tregs, HIV-primed mLCs and human epidermal LCs significantly impaired the induction of FoxP3hiCD45RA- effector Tregs than HIV-unprimed mLCs and human epidermal LCs. CONCLUSIONS: HIV-primed LCs trigger beneficial immune responses against HIV infection through the increased induction of HIV-specific CD8+ T cells and the decreased induction of effector Tregs in the initial phase of HIV infection, thereby contributing to the prolonged onset of AIDS.
Authors: David J Delgado-Diaz; David Tyssen; Joshua A Hayward; Raffi Gugasyan; Anna C Hearps; Gilda Tachedjian Journal: Front Cell Infect Microbiol Date: 2020-01-10 Impact factor: 5.293