HIV coinfection impairs CD28-mediated costimulation of hepatitis C virus-specific CD8 cells.
BACKGROUND
During human immunodeficiency virus (HIV) infection, reduced proportions of CD8 cells express CD28, the key costimulatory molecule for lymphocyte activation. However, it is unclear whether reduced CD28 expression affects immune responses to non-HIV antigens, potentially contributing to susceptibility to opportunistic infection.


METHODS
We measured CD4- and CD8-specific interferon- gamma responses to hepatitis C virus (HCV) peptide pools in subjects with chronic HCV monoinfection (n=14), in subjects with chronic HCV/HIV coinfection (n=15), and in healthy control subjects (n=10) by enzyme-linked immunospot assay in the presence and absence of CD28 costimulation.


RESULTS
Anti-CD28 agonist increased the cumulative frequency of HCV-specific CD4 cell responses in the subjects with HCV monoinfection and in those with HCV/HIV coinfection. In contrast, anti-CD28 agonist increased the breadth and cumulative frequency of HCV-specific CD8 cell responses only in the subjects with HCV monoinfection. Additionally, in the presence of anti-CD28 agonist, the proportion of subjects responding, the cumulative frequency, and the breadth of reactive CD8 cells were greater among the subjects with HCV monoinfection than among those with HCV/HIV coinfection. Finally, the HCV/HIV-coinfected subjects had lower proportions of CD8 cells that expressed CD28.


CONCLUSIONS
These results indicate that, during HCV/HIV coinfection, memory-effector CD8 cells have reduced responsiveness to CD28 costimulation. This appears to reflect a global effect that HIV has on the activation or differentiation state of CD8 cells that are responsive to other microbial pathogens. This functional defect has implications for the pathogenesis of HCV/HIV coinfection.
Yonkers
Nicole L
NL
Department of Medicine, Cleveland Veterans Administration Medical Center, Center for AIDS Research and University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH 44106, USA.
Rodriguez
Benigno
B
Post
Anthony B
AB
Asaad
R
R
Jones
Linda
L
Lederman
Michael M
MM
Lehmann
Paul V
PV
Anthony
Donald D
DD
D000328:Adult; D018106:CD28 Antigens / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged
D018106:CD28 Antigens; D007371:Interferon-gamma