Antiviral effect and ex vivo CD4(+) T cell proliferation in HIV-positive patients as a result of CD28 costimulation

Because stimulation of CD4(+) lymphocytes leads to activation of human immunodeficiency virus-type 1 (HIV-1) replication, viral spread, and cell death, adoptive CD4(+) T cell therapy has not been possible. When antigen and CD28 receptors on cultured T cells were stimulated by monoclonal antibodies (mAbs) to CD3 and CD28 that had been immobilized, there was an increase in the number of polyclonal CD4(+) T cells from HIV-infected donors. Activated cells predominantly secreted cytokines associated with T helper cell type 1 function, The HIV-1 viral load declined in the absence of antiretroviral agents, Moreover, CD28 stimulation of CD4(+) T cells from uninfected donors rendered these cells highly resistant to HIV-I infection, Immobilization of CD28 mAb was crucial to the development of HIV resistance, as cells stimulated with soluble CD28 mAb were highly susceptible to HIV infection, The CD28-mediated antiviral effect occurred early in the viral life cycle, before HIV-1 DNA integration. These data may facilitate immune reconstitution and gene therapy approaches in persons with HIV infection.