The goal of this project is to gain understanding of the regeneration and immunobiologic capacities of the CD4+ T cells in HIV-1 infected subjects, and to explore their implication for immune recovery. Given the ravages of HIV-1 infection on CD4 positive T cells, the investigator hypothesized that the regenerative capacity and repertoire will progressively diminish as the disease advances. Alternatively, if CD4 positive T cells have an inexhaustible ability to regenerate, the expansion capacity and repertoire may be maintained. Distinguishing between these possibilities have a strong implication as to the extent of immunologic recovery when effective anti-retroviral therapy is instituted. In the current project, the first specific aims include experiments designed to determine the expansion capacity of CD4 positive T cells from patients at various stages of HIV-1 infection. Subjects are sub-divided into groups with high and low viral loads. The regenerative capacity will be compared with the regenerative capacity of CD4+ T cells from uninfected subjects and infected, long term non-progressors. In the second aim, experiments will examine the immunobiological repertoire and function of CD4+ T cells as they advance through repetitive mitotic divisions. Preservation of the immunobiologic function through all cell divisions bode well for both the extent and duration of immunologic recovery after virus replication is halted. In the third specific aim, a selected sub-groups of subjects with very low CD4 T cell counts will be examined to determine the regenerative and immunobiologic capacities before and after they have received potent anti-retroviral therapy. These studies will be assessed longitudinally. This will provide evidence as to whether stopping the ravages of viral infection will permit gradual return of cells with high regenerative capacity as might be expected if new CD4 positive T cells are thymic derived.
In specific aim four, the clinical significance of the regenerative capacity will be determined.