title: Differential effects of HIV transmission from monocyte-derived dendritic cells vs. monocytes to IL-17+CD4+ T cells.
abstract: HIV infection leads to CD4 helper T cell (Th) loss, but not all Th cells are equally depleted. The contribution of other immune cells in the Th depletion also remains unclear. This study investigates HIV transmission from monocyte-derived dendritic cells (MDDCs) vs. monocytes to Th17 and Th1 cells using an allogeneic coculture model. The addition of HIV to MDDCs increased the expression of the negative regulatory molecule PD-L1 and decreased the expression of the activation markers HLA-DR and CD86, whereas the virus up-regulated HLA-DR and CD86, but not PD-L1, on monocytes. Coculturing of CD4+T cells with MDDCs pretreated with HIV led to the decline of Th17, but not Th1, responses. In contrast, pretreatment of monocytes with HIV increased Th17 without affecting Th1 responses. The enhanced Th17 responses in the cocultures with HIV-treated monocytes were also accompanied by high numbers of virus-infected CD4+T cells. The Th17 expansion arose from memory CD4+T cells with minimal contribution from naïve CD4+T cells. The Th17-enhancing activity was mediated by the HIV envelope and did not require productive virus infection. Comparison of MDDCs and monocytes further showed that, although HIV-treated MDDCs reduced Th proliferation and increased the activation of the apoptosis mediator caspase-3, HIV-treated monocytes enhanced Th proliferation without increasing the active caspase-3 levels. This study indicates the potential role of distinct myeloid cell populations in shaping Th17 responses during HIV infection.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Yu-Ya
authors.initials: YY
authors.lastname: Mitsuki
authors.affiliation: Veterans Affairs New York Harbor Healthcare System, Manhattan, New York, USA.|Department of Pathology, New York University Langone Medical Center, New York, New York, USA; and.
authors.forename: Michael
authors.initials: M
authors.lastname: Tuen
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA; catarina.hioe@mssm.edu.|James J. Peters Veterans Affairs Medical Center, Bronx, New York, USA.
authors.forename: Catarina E
authors.initials: CE
authors.lastname: Hioe
mesh_terms: D017209:Apoptosis; D051940:B7-2 Antigen / Q000378:metabolism; D060890:B7-H1 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000502:physiology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D015854:Up-Regulation
chemical_list: D051940:B7-2 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D015699:HIV Envelope Protein gp120; D006684:HLA-DR Antigens; D020381:Interleukin-17
keywords: HIV envelope; Th1; Th17