Inhibition of R5‐tropic HIV type‐1 replication in CD4+ natural killer T cells by γδ T lymphocytes |
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Authors: | Kyoko Omi Masumi Shimizu Eri Watanabe Jiro Matsumura Chizuno Takaku Eiji Shinya Hidemi Takahashi |
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Institution: | Department of Microbiology and Immunology, Nippon Medical School, , Tokyo, Japan |
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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. |
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Keywords: | CD4+ natural killer T cells CD8α α + cells HIV‐1 p24 R5‐tropic HIV‐1 viral replication γ δ T cells |
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