Differential effects of CD28 costimulation on HIV production by CD4+ cells.
We have observed that CD28 costimulation of CD4+ cells can have differential effects on HIV replication. Triggering the CD28 molecule on peripheral blood CD4+ cells during stimulation with anti-CD3 Abs enhances virus production following acute infection with HIV. Endogenous virus production in CD4+ cells from HIV-infected individuals is also increased by this procedure. The enhanced virus production occurs equally when anti-CD28 Abs and soluble forms of the natural ligands for CD28, CD80Ig, and CD86Ig are used to trigger CD28 on CD4+ cells during stimulation. This increased virus replication is observed only when the source of CD28 costimulation is removed immediately after stimulation and before infection. Continual exposure of CD4+ cells to anti-CD3 and CD28 Ab beads following acute infection prevents virus production. These findings may have relevance to therapeutic approaches aimed at inhibiting HIV replication by CD28 costimulation.
Barker
E
E
Department of Medicine, University of California, San Francisco 94143-1270, USA.
Bossart
K N
KN
Levy
J A
JA
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000494:pharmacology; D018122:B7-1 Antigen / Q000276:immunology / Q000494:pharmacology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology*; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006678:HIV / Q000254:growth & development / Q000276:immunology* / Q000502:physiology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology; D014779:Virus Replication / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; C497964:CD86 protein, human; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins