Antiviral effect from the CD28 costimulatory receptor mediates ex vivo CD4+ T cell expansion from patient with HIV-1 infection.
Int Conf AIDS 1996 Jul 7-12; 11:222 (abstract no. Tu.A.271) St Louis DC, Levine B, Mosca J, Riley J, Carroll R, Lin JT, Vahey M, Jagodzinski L, Wagner K, Mayers D, Burke D, Weislow O, June C, Henry M; Henry M. Jackson Foundation, Rockville, MD, USA. Fax: 301-762-7460. E-mail: dstlouis@pasteur.hjf.org.
Human immunodeficiency virus type 1 (HIV-1) infection is associated with a progressive decline in CD4+ lymphocytes. Because stimulation of CD4+ lymphocytes leads to activation of HIV-1 replication, viral spread and cell death, adoptive CD4+ cell therapeutic strategies have not been possible. We report here that CD28 receptor costimulation can lead to polyclonal expansion of CD4+ cell from HIV-infected donors during cell culture. Activated cells secreted predominately cytokines associated with T helper type 1 function. HIV-1 specific expression and proviral DNA load declined during culture. Surprisingly, the addition of antiretroviral agents to cell cultures was not required. Moreover, CD28 stimulation rendered CD4+ cell from uninfected donors highly resistant to HIV-1 infection. The mechanism responsible for the anti-HIV effect was related to the mode of T cell activation by anti-CD28. While CD4+ cells stimulated with immobilized anti-CD28 were resistant to HIV infection, cells stimulated with soluble anti-CD28 were highly susceptible to HIV infection. The CD28-mediated antiviral effect was early in the viral life cycle, prior to HIV-1 DNA integration. In contrast, CD28 costimulation renders CD4+ lymphocytes highly permissive to retroviral vector transduction. The transduced lymphocytes can be enriched to purify in culture, and greater than five logs of cell expansion can be achieved. These data may facilitate immune reconstitution and gene therapy approaches in persons with HIV infection.
Keywords: AEGIS, Antigens, CD28, Antigens, CD4, HIV Infections, T-Lymphocytes, HIV-1, CD4-Positive T-Lymphocytes, Virus Replication, HIV, Cytokines, HIV Core Protein p24, Anti-HIV Agents, Human, virology, ICA11
