VANCOUVER, BC--Expansion of CD4+ cells could help reconstitute the immune system in patients with AIDS. However, this approach has been unfeasible because stimulation of a patient's CD4+ cells to replicate also leads to HIV replication and greater cell death.
Now, Bruce L. Levine, PhD, and colleagues at the Naval Medical Research Institute have identified a CD28-mediated effect that may permit the generation of large numbers of CD4+ T cells without increased HIV replication.
Dr. Levine reported at the 11th International Conference on AIDS that ex vivo co-stimulation of the CD28 receptor on CD4+ T cells can lead to polyclonal expansion of CD4+ cells from HIV-infected donors, resulting in a large stock of new uninfected CD4+ T cells.
Activated cells secreted predominantly cytokines associated with T helper type I function. HIV-1 specific expression and proviral DNA load declined during culture, Dr. Levine said.
"Our results demonstrate that proliferation of polyclonal HIV-1 uninfected CD4+ T cells from HIV-infected donors is possible," he noted. This effect occurred without the use of antiretroviral drugs.
CD28 stimulation also made unin-fected CD4+ T cells "highly resistant to HIV-1 infection," Dr. Levine said. This effect did not require the presence of CD8+ cells, and it was dependent on how the CD28 receptor was activated.
Exposure to immobilized anti-CD28 antibodies made CD4+ T cells resistant to HIV, but stimulation with soluble anti-CD28 made them more susceptible to infection.