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
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.