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Updated: Jan 5, 2026
In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
T cells with high PD-1 expression are associated with lower HIV-specific immune responses despite long-term
Bernard J C Macatangay1, Rajesh T Gandhi, Richard B Jones
1Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts Division of Infectious Diseases, Weill Cornell Medicine, New York, New York Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania Social & Scientific Systems, Inc., Silver Spring, Maryland Department of Medicine, University of North Carolina, Chapel Hill, North Carolina Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Objective:
We evaluated frequencies of T cells with high PD-1 expression (PD-1) before and after long-term effective antiretroviral therapy (ART), and determined if frequencies on-ART correlated positively with measures of HIV persistence and negatively with HIV-specific responses.
Methods:
We enrolled individuals who started ART during chronic infection and had durable suppression of viremia for at least 4 years (N = 99). We assessed PD-1 T-cell frequencies at timepoints pre-ART and on-ART using flow cytometry, and evaluated how frequencies on-ART are associated with measures of HIV persistence, HIV-specific immune responses, and immune activation levels.
Results:
Pre-ART, PD-1 CD4 T cells correlated positively with viremia and negatively with CD4 T-cell count. At year 1 on-ART, %PD-1 CD4 T cells decreased but then remained stable at 4 and 6-15 years on-ART, whereas %PD-1 CD8 T cells on-ART remained similar to pre-ART. PD-1 CD4 T cells correlated positively with HIV DNA pre-ART and on-ART, and with CD4 T-cell activation on-ART. PD-1 CD4 T cells negatively correlated with HIV Gag-specific and Env-specific T-cell responses but not with CMV-specific or EBV-specific responses. PD-1 CD8 T cells trended towards a negative correlation with responses to Gag and Env, but not to CMV and EBV.
Conclusion:
PD-1 T cells persist in blood despite prolonged suppression on ART, correlate with HIV DNA levels, and are associated with lower HIV-specific T-cell responses but not CMV-specific or EBV-specific responses, suggesting that these cells are HIV-specific. The findings support evaluating PD-1 blockade strategies for their effect on HIV persistence and HIV-specific immunity.
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