Related Experiment Video
Updated: Jul 14, 2026
In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 16, 2013
'Modeling' relationships among HIV-1 replication, immune activation and CD4+ T-cell losses using adjusted correlative
M M Lederman1, L A Kalish, D Asmuth
1Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. Lederman.Michael@clevelandactu.org
Objective:
To model the relationships among HIV-1 replication, immune activation and CD4+ T-cell losses in HIV-1 infection.
Methods:
Cross-sectional analysis of baseline data from the Viral Activation by Transfusion Study. Comparisons of unadjusted and adjusted correlative analyses to establish models for mechanisms of cell loss in AIDS.
Results:
Using these analyses, significant correlations were found among plasma levels of tumor necrosis factor alpha (TNFalpha) and its type two receptor (TNFrII), interleukin-6 (IL-6), beta2-microglobulin, expression of CD38 and HLA-DR on CD8+ T lymphocytes and plasma levels of HIV-1 RNA. When correlations among these indices were adjusted for possible intermediary correlations, the relationship between HIV-1 RNA levels and all plasma markers of immune activation could be accounted for by the correlation between plasma HIV-1 RNA and plasma TNFrII levels. In addition, the negative correlations that both HIV-1 RNA levels and TNFrII levels had with CD4+ T-cell counts were partially accounted for by the correlations of HIV-1 RNA and TNFrII with CD38 expression on CD8+ T cells. In persons with advanced disease (CD4+ T cells < 50 x 10(6)/l) IL-6 levels were inversely correlated with CD4+ T-cell counts.
Conclusions:
This analysis is consistent with a model wherein HIV-1 replication induces TNFalpha expression that induces multiple other indices of immune activation. In this model, HIV-1 replication and TNFalpha expression induce CD4+ T-cell losses at least in part through mechanisms reflected in heightened CD38 expression.
