Phosphoantigen-reactive V gamma 9V delta 2 T lymphocytes suppress in vitrohuman immunodeficiency virus type 1 replication by cell-released antiviralfactors including CC chemokines

V gamma 9V delta 2 T lymphocytes are broadly reactive against various intra cellular pathogens and display both lytic and proliferative responses to hu man immunodeficiency virus (HIV)-infected cells. HIV infection of periphera l blood mononuclear cell cultures led to absolute increases in V gamma 9V d elta 2 T cells accompanied by decreased p24 levels. Strong ya T cell activa tion with nonpeptidic mycobacterial phosphoantigens (TUBAg1 extract or synt hetic isopentenyl pyrophosphate) resulted in potent inhibition of HIV repli cation through soluble released factors. Subsequent analyses showed that ph osphoantigen-activated gamma delta T cells produced substantial amounts of beta-chemokines (macrophage inflammatory protein [MIP]-1 alpha, MIP-1 beta, and regulated-on-activation, normal T-cell-expressed and -secreted beta-ch emokine [RANTES]), which represent the natural ligand for the CCR5 HIV core ceptor, Accordingly, anti-beta-chemokine antibodies neutralized the inhibit ion of monocytotropic HIV strains by ya T cell-released factors. Moreover, a T-tropic HIV strain using the CXCR4 coreceptor for virus entry was po ten try inhibited. Together, these data reveal that phospho antigen-activated gamma delta T cells are an important source of CC chemokines and may suppre ss HIV replication through cell-released antiviral factors.