title: Inhibition of R5-tropic HIV type-1 replication in CD4⁺ natural killer T cells by γδ T lymphocytes.
abstract: After the development of highly active anti-retroviral therapy, it became clear that the majority of emergent HIV-1 is macrophage-tropic and infects CD4⁺, CCR5-expressing cells (R5-tropic). There are three distinct cell populations, R5-tropic, HIV-1-susceptible CD4⁺ cells: (i) natural killer T (NKT) cells, (ii) dendritic cells and macrophages, and (iii) tissue-associated T cells residing primarily at mucosal surfaces. We have confirmed that CD4⁺ NKT cells derived from peripheral blood mononuclear cells (PBMCs) predominantly express CCR5 rather than CXCR4, whereas the reverse is true for CD4⁺ T cells derived from circulating PBMCs, and that R5-tropic HIV-1 expands efficiently in the CD4⁺ NKT cells. Moreover, when PBMCs depleted of CD8α⁺ cells were stimulated in the presence of α-galactosylceramide (α-GalCer) and R5-tropic HIV-1 [NL(AD8)], the production of HIV-1 virions was not suppressed, whereas, similar to the untreated PBMCs, depletion of CD8β⁺ cells from PBMCs significantly inhibited virion production. These findings suggest that CD8αα⁺ but not CD8αβ⁺ cells may have the ability to inhibit R5-tropic HIV-1 replication in CD4⁺ NKT cells. Here, we show that co-culturing R5-tropic HIV-1-infected CD4⁺ NKT cells with CD8αα⁺ γδ T cells, in particular Vγ1Vδ1 cells, but not with CD8αα⁺ NKT cells or CD8αα⁺ dendritic cells, inhibits HIV-1 replication mainly by secreting chemokines, such as macrophage inflammatory proteins 1α and 1β and RANTES. Collectively, these results indicate the importance of CD8αα⁺ γδ T cells in the control of R5-tropic HIV-1 replication and persistence in CD4⁺ NKT cells.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Omi
authors.forename: Masumi
authors.initials: M
authors.lastname: Shimizu
authors.forename: Eri
authors.initials: E
authors.lastname: Watanabe
authors.forename: Jiro
authors.initials: J
authors.lastname: Matsumura
authors.forename: Chizuno
authors.initials: C
authors.lastname: Takaku
authors.forename: Eiji
authors.initials: E
authors.lastname: Shinya
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D018920:Coculture Techniques; D005699:Galactosylceramides / Q000494:pharmacology; D015497:HIV-1 / Q000254:growth & development* / Q000276:immunology / Q000472:pathogenicity; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000378:metabolism*; D013997:Time Factors; D014779:Virus Replication
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C483024:CCL5 protein, human; C584933:CCR5 protein, human; D018946:Chemokine CCL5; D005699:Galactosylceramides; D015395:Histocompatibility Antigens Class I; C493277:MAPKAP1 protein, human; C099187:MHC class I-related chain A; C098080:MICB antigen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019713:Receptors, CCR5; C493154:alpha-galactosylceramide
keywords: CD4+ natural killer T cells; CD8αα+ cells; HIV-1 p24; R5-tropic HIV-1; viral replication; γδ T cells