Single-Cell Level Response of HIV-Specific and Cytomegalovirus-Specific CD4 T Cells Correlate With Viral Control in Chronic HIV-1 Subtype A Infection
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Date
2012
Journal Title
Journal ISSN
Volume Title
Publisher
JAIDS Journal of Acquired Immune Deficiency Syndromes
Abstract
HIV-1 subtype A is the second
most prevalent subtype globally and is associated with reduced viral
load, higher CD4 absolute counts, and slower disease progression.
To study the possible role of T cells associated with better outcome,
we examined CD4 and CD8 T-cell responses against HIV-1 and
cytomegalovirus (CMV) in Ugandans infected with subtype A HIV-1.
Methods: T-cell responses were investigated using flow cytometry
and novel subtype A variant inclusive peptide (VIP) sets designed
for this evaluation. CD4 T-cell responses focused primarily on Gag,
whereas CD8 T-cell responses were broadly directed against Gag,
gp41, and Nef VIP sets. CD4 T cells primarily responded with
interferon (IFN)-g, whereas CD8 cells were more diverse with
degranulation (CD107a), IFN-g, and macrophage inflammatory protein
(MIP)-1b production.
Results: No relationship was observed between CD8 T-cell
responses and the HIV-1 load. Similarly, the frequency of CD4 T
cells responding to these antigens did not associate with viral
control. However, in CD4 T cells responding against Gag or CMV,
the IFN-g intensity, indicative of the production at the singlecell
level, was inversely proportional to viral load. No significant
relationship was found between T-cell effector/memory phenotype
and viral control.
Conclusions: The per cell production of IFN-g in CD4 T cells
responding to HIV-1 or CMV correlated with viral control in chronic
HIV-1 subtype A infection. These data suggest that quantitative
aspects at the single-cell level may be more important than the
frequency of antigen-specific CD4 T cells in HIV-1 subtype A infection
control.
Description
Keywords
T cells, HIV-1, AIDS, Viral infections, Memory
Citation
Eller, M. A., Eller, L. A., Ratto-Kim, S., Ouma, B. J., Lo, V., de Souza, M., ... & Currier, J. R. (2012). Single-cell level response of HIV-specific and cytomegalovirus-specific CD4 T cells correlate with viral control in chronic HIV-1 subtype A infection. JAIDS Journal of Acquired Immune Deficiency Syndromes, 61(1), 9-18.