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[CD8.sup.+] T cells are critical for effective host defenses against viral infections. Studies addressing HIV-induced immune responses in infected individuals have suggested that [CD8.sup.+] T cells play an important role in controlling viral replication. However, despite an abundance of HIV-specific [CD8.sup.+] 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.sup.+] T cells expressing CD38. Previous studies have demonstrated that the expression of CD38 on [CD8.sup.+] 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.sup.+] T cells is unclear. We demonstrate a correlation between levels of HIV-specific [CD8.sup.+] T cells and levels of [CD8.sup.+] T cells expressing CD38 in untreated patients. The distribution of HIV-specific [CD8.sup.+] T cells was heavily skewed toward [CD38.sub.+] [CD8.sup.+] T cells in patients with a high percentage of [CD38.sup.+][CD8.sup.+] T cells. Spontaneous/Fas-mediated apoptosis in [CD38.sup.+][CD8.sup.+] T cells was significantly higher in patients with high percentages of [CD38.sup.+][CD8.sup.+] T cells. Our data suggest that a substantial proportion of the HIV-specific [CD8.sup.+] T cells present in [CD38.sup.+][CD8.sup.+] 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.sup.+] T cells in such 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+ I 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. [ABSTRACT FROM AUTHOR]