V3 induces in human normal cell populations an accelerated macrophage-mediated proliferation--apoptosis phenomenon of effector T cells when they respond to their cognate antigen.
The semi-conserved domain of V3 of HIV-1 was synthesised in a lipopeptide form to be presented on the surface of liposome particles. Composite liposomes were constructed with entrapped tetanus toxoid as a recall antigen (lipo-V3/TT liposomes) to study the influence of V3 on effector T cells of human normal peripheral lymphocyte populations. We demonstrated that lipo-V3/TT liposomes induce a V3-specific response characterised by an early, enhanced proliferation of effector CD4+ T cells, followed by a sharp apoptosis. The phenomenon required the presence of monocyte-derived macrophages and CD4+ T cells, but it was qualitatively and quantitatively distinct from the normal soluble antigen-mediated antigen presenting cell: T cell interaction. Presence of the beta-chemokine RANTES in the culture medium inhibited the phenomenon, suggesting that V3 plays a costimulatory role that involves the chemokine receptor CCR5 pathway during the process of antigen presentation to T cells. This observation may be very important if it occurs also in HIV-1 infection, as it may explain the selective and progressive depletion of non-infected effector CD4+ T cells.
Zafiropoulos
A
A
Department of Applied Biochemistry and Immunology, Institute of Molecular Biology and Biotechnology, Vassilika Vouton, Heraklion, Crete, Greece.
Baritaki
S
S
Sioumpara
M
M
Spandidos
D A
DA
Krambovitis
E
E
D018941:Antigens, CD19 / Q000378:metabolism; D017209:Apoptosis; D015704:CD4 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002455:Cell Division; D018946:Chemokine CCL5 / Q000494:pharmacology; D003470:Culture Media / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008214:Lymphocytes / Q000737:chemistry / Q000276:immunology; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D019713:Receptors, CCR5 / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D013745:Tetanus Toxoid / Q000276:immunology; D013997:Time Factors
D018941:Antigens, CD19; D015704:CD4 Antigens; D016827:CD8 Antigens; D018946:Chemokine CCL5; D003470:Culture Media; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D008081:Liposomes; D010446:Peptide Fragments; D019713:Receptors, CCR5; D013745:Tetanus Toxoid