Phosphoantigen-reactive Vγ9Vδ2 T lymphocytes suppress in vitro human immunodeficiency virus type 1 replication by cell-released antiviral factors including CC chemokines

Vγ9Vδ2 T lymphocytes are broadly reactive against various intracellular pathogens and display both lyric and proliferative responses to human immunodeficiency virus (HIV)-infected cells. HIV infection of peripheral blood mononuclear cell cultures led to absolute increases in Vγ9Vδ2 T cells accompanied by decreased p24 levels. Strong γδ T cell activation with nonpeptidic mycobacterial phosphoantigens (TUBAg1 extract or synthetic isopentenyl pyrophosphate) resulted in potent inhibition of HIV replication through soluble released factors. Subsequent analyses showed that phosphoantigen-activated γδ T cells produced substantial amounts of β- chemokines (macrophage inflammatory protein [MIP]-1α, MIP-1β, and regulated-on-activation, normal T-cell-expressed and -secreted beta-chemokine [RANTES]), which represent the natural ligand for the CCR5 HIV coreceptor. Accordingly, anti-β-chemokine antibodies neutralized the inhibition of monocytotropic HIV strains by γδ T cell-released factors. Moreover, a T- tropic HIV strain using the CXCR4 coreceptor for virus entry was potently inhibited. Together, these data reveal that phosphoantigen-activated γδ T cells are an important source of CC chemokines and may suppress HIV replication through cell-released antiviral factors.