VANCOUVER, BC--CD8+ T cells appear to play a central role in the body's strategy for fighting HIV, particularly in those patients known as long-term non-progressors or long-term survivors who remain well for many years despite being infected with HIV.
New research presented at the 11th International Conference on AIDS suggests two separate mechanisms by which CD8+ cells suppress HIV, but the specific suppressive factor (or factors) secreted by CD8 has not yet been identified.
Work by Drew Weissman, MD, PhD, and his colleagues at the NIH show that CD8+ T cells function differently in HIV-infected subjects than in uninfected controls. These researchers developed an in vitro system that models the paracortical region of the lymph node by using dendritic cells to activate CD4+ T cells (without additional mitogen). This mimics the situation in the lymph nodes where most HIV replication and spread are now thought to occur.
Dr. Weissman tested CD8+ cell activity in two systems. One used dendritic cells and CD4+ T cells from uninfected people. Their T cells were pulsed with HIV as an "acute infection" model. The other approach used dendritic cells and CD4+ T cells from HIV-infected subjects as an "endogenous infection" model. In both models, CD8+ T cells were added at the initiation of culture.
The CD8+ cells produced two forms of suppressive activity. One factor suppressed HIV replication in chronically infected CD4+ T cells. This factor was produced by CD8+ T cells from both infected and uninfected subjects, but the ability to produce it appears to be lost as HIV infection progresses.
The second factor suppressed HIV replication during acute infection. It was produced only by CD8+ from HIV- infected subjects. This suppressive activity was seen even in CD8+ cells from patients with advanced HIV disease.
CD8+ cells from uninfected subjects actually enhanced viral replication. Pretreatment of CD8+ cells with gamma irradiation wiped out the suppressive factor that blocks acute HIV infection but not the one that blocks HIV replication in chronically infected cells.