HIV coinfection impairs CD28-mediated costimulation of hepatitis C virus-specific CD8 cells.

TitleHIV coinfection impairs CD28-mediated costimulation of hepatitis C virus-specific CD8 cells.
Publication TypeJournal Article
Year of Publication2006
AuthorsYonkers NL, Rodriguez B, Post AB, Asaad R, Jones L, Lederman MM, Lehmann PV, Anthony DD
JournalJ Infect Dis
Volume194
Issue3
Pagination391-400
Date Published2006 Aug 1
ISSN1537-6613
KeywordsAdult, Antigens, CD28, CD8-Positive T-Lymphocytes, Female, Hepacivirus, Hepatitis C, HIV, HIV Infections, Humans, Interferon-gamma, Male, Middle Aged
Abstract

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.

DOI10.1086/505582
Alternate JournalJ. Infect. Dis.
PubMed ID16826489
Grant ListAI36219 / AI / NIAID NIH HHS / United States
R01 DK068361 / DK / NIDDK NIH HHS / United States
R01AI47839 / AI / NIAID NIH HHS / United States