Antiviral Effect and Ex Vivo CD4 + T Cell Proliferation in HIV-Positive Patients as a Result of CD28 Costimulation

• DOI: 10.1126/science.272.5270.1939
• Publication Date: 2006-10-27T18:30:41Z
• Authors: Bruce L. Levine; Joseph D. Mosca; James L. Riley; Richard G. Carroll; Maryanne T. Vahey; Linda L. Jagodzinski; Kenneth F. Wagner; Douglas L. Mayers; Donald S. Burke; Owen S. Weislow; Daniel C. St. Louis; Carl H. June
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; CD3 Complex; Virus Integration; Antibodies, Monoclonal; HIV Infections; Lymphocyte Activation; Virus Replication; CD4 Lymphocyte Count; 3. Good health; 03 medical and health sciences; CD28 Antigens; HIV-1; Cytokines; Humans; Interleukin-2; Chemokines; Phytohemagglutinins; Cell Division; Cells, Cultured

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-1 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.