HIV-1–specific CD8+ T cells can mature to memory in patients receiving ART. Part 2
Patients 4480, SP1549, 4496, and 4170 were included in this statistical analysis as we did have reliable data regarding time since the last positive PVL test for these patients. A significant correlation was observed between the length of time since the last positive Ultrasensitive test and egress of cells from the acute subset. The percentage of memory versus time (r=0.54) was not significant, which could reflect the fact that some of these patients had a substantial proportion of cells in the intermediate stage. No correlation was found between either PVLs or CD4+ T cell counts at the start of ART and the maturation of cells (data not shown). These results suggest that, if there were a high degree of control for a sustained period, HIV-1–specific CD8+ T cells would mature to memory cells.
Longitudinal analyses of subset distributions in patients receiving ART confirm that antigen load determines the maturation stateWe measured longitudinally the subset distribution for 4 patients, 3 before and after the initiation of ART and the 1 patient while receiving ART and then after discontinuing ART. For the 3 patients initiating therapy, a proportion of the HIV-1–specific T cells matured to memory as the PVL declined. For the 2 patients receiving ART for >1 month, this proportion increased as a function of the time that the virus is controlled. For the 1 patient discontinuing ART, the cells shifted toward the acute-phase phenotype as the PVL increased.
The models of viral infection used in this study were chosen because they reflect a variety of outcomes and therefore allow us to explore the relationship between antigen burden and T cell maturation. FLU was chosen as an example of an acute/resolved infection, in which there should be no antigen load. EBV and CMV are both herpesviruses, but they differ fundamentally in their strategies for maintaining virus reservoirs, which would lead to differences in antigen load. EBV is a γ-herpesvirus that is able to drive clonal expansion of latently infected B cells and consequently maintain a latent pool with minimal viral replication. CMV is a β-herpesvirus that persistently replicates. Therefore, the relative antigen load is likely to be lower for EBV than for CMV. Additional indirect support for these differences in antigen load derives from the differences in the levels of antigen-specific CD8+ T cells that were, on average, higher for CMV (mean, 1.9%; range, 0.4%–5% of CD8+ cells) than for EBV (mean, 0.52%; range, 0.2%–1.7% of CD8+ cells). In addition, we studied a panel of HIV-1–infected patients representing a range of control over the virus.