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.