Phosphoantigen-reactive Vgamma9Vdelta2 T lymphocytes suppress in vitro human immunodeficiency virus type 1 replication by cell-released antiviral factors including CC chemokines.
Vgamma9Vdelta2 T lymphocytes are broadly reactive against various intracellular pathogens and display both lytic and proliferative responses to human immunodeficiency virus (HIV)-infected cells. HIV infection of peripheral blood mononuclear cell cultures led to absolute increases in Vgamma9Vdelta2 T cells accompanied by decreased p24 levels. Strong gammadelta 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 gammadelta T cells produced substantial amounts of beta-chemokines (macrophage inflammatory protein [MIP]-1alpha, MIP-1beta, 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-beta-chemokine antibodies neutralized the inhibition of monocytotropic HIV strains by gammadelta 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 gammadelta T cells are an important source of CC chemokines and may suppress HIV replication through cell-released antiviral factors.
Poccia
F
F
International Center for AIDS and Emerging Infections, Institute for Infectious Diseases "L. Spallanzani,", 00149 Rome, Italy. poccia@uniroma2.it
Battistini
L
L
Cipriani
B
B
Mancino
G
G
Martini
F
F
Gougeon
M L
ML
Colizzi
V
V
D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology*; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000096:biosynthesis* / Q000276:immunology; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000502:physiology*; D045782:Hemiterpenes; D006801:Humans; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000276:immunology; D009161:Mycobacterium / Q000276:immunology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010750:Phosphoproteins / Q000276:immunology / Q000494:pharmacology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D014779:Virus Replication
D000942:Antigens, Bacterial; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D016655:HIV Core Protein p24; D045782:Hemiterpenes; D019402:Macrophage Inflammatory Proteins; D009943:Organophosphorus Compounds; D010750:Phosphoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C004809:isopentenyl pyrophosphate