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.
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. twchun@nih.gov
Tae-Wook
TW
Chun
J Shawn
JS
Justement
Christina
C
Sanford
Claire W
CW
Hallahan
Marie A
MA
Planta
Mona
M
Loutfy
Shyam
S
Kottilil
Susan
S
Moir
Colin
C
Kovacs
Anthony S
AS
Fauci
D036541:ADP-ribosyl Cyclase / Q000235:genetics / Q000276:immunology; D051997:ADP-ribosyl Cyclase 1; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000821:virology*; D003587:Cytomegalovirus / Q000302:isolation & purification; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008562:Membrane Glycoproteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D014766:Viremia / Q000276:immunology
D015703:Antigens, CD; D015415:Biomarkers; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1