Inhibition of R5-tropic HIV type-1 replication in CD4? natural killer T cells by γδ T lymphocytes.

摘要

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.