Inhibition of R5-tropic HIV type-1 replication in CD4+natural killer T cells by cd T lymphocytes

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 CD8(+) cells were stimulated in the presence of -galactosylceramide (-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 CD8(+) cells from PBMCs significantly inhibited virion production. These findings suggest that CD8(+) but not CD8(+) 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 CD8(+)T cells, in particular V1V1 cells, but not with CD8(+) NKT cells or CD8(+) dendritic cells, inhibits HIV-1 replication mainly by secreting chemokines, such as macrophage inflammatory proteins 1 and 1 and RANTES. Collectively, these results indicate the importance of CD8(+)T cells in the control of R5-tropic HIV-1 replication and persistence in CD4(+) NKT cells.