Relationship between the frequency of HIV-specific CD8+ T cells and the level of CD38+CD8+ T cells in untreated HIV-infected individuals

CD8(+) T cells are critical for effective host defenses against viral infections. Studies addressing HIV-induced immune responses in infected individuals have suggested that CD8(+) T cells play an important role in controlling viral replication. However, despite an abundance of HIV-specific CD8(+) T cells, HIV is not contained in many untreated patients. Active HIV replication is associated with numerous immunologic changes, the most notable and consistent of which is an increase in CD8(+) T cells expressing CD38. Previous studies have demonstrated that the expression of CD38 on CD8(+) T cells is associated with poor prognostic outcome in infected individuals with detectable plasma viremia; however, the relationship between the expression of CD38 and the frequency of HIV-specific CD8(+) T cells is unclear. We demonstrate a correlation between levels of HIV-specific CD8(+) T cells and levels of CD8(+) T cells expressing CD38 in untreated patients. The distribution of HIV-specific CD8(+) T cells was heavily skewed toward CD38(+)CD8(+) T cells in patients with a high percentage of CD38(+)CD8(+) T cells. Spontaneous/Fas-mediated apoptosis in CD38(+)CD8(+) T cells was significantly higher in patients with high percentages of CD38(+)CD8(+) T cells. Our data suggest that a substantial proportion of the HIV-specific CD8(+) T cells present in CD38(+)CD8(+) T cells in patients with active viral replication arise by HIV-driven aberrant immune activation and may not manifest effective cytolytic activity against infected targets due to a high degree of susceptibility to apoptosis, thus providing an explanation of why HIV is not successfully contained by CD8(+) T cells in such individuals.