Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection leads to severe systemic inflammation, increasing non-AIDS morbidity and mortality risk. CD39 ectoenzyme on T-cells, which catalyzes the conversion of pro-inflammatory purines to immunosuppressive adenosine, plays an important role in inflammation control. The role of CD39 + T-cells in systemic inflammation during HIV/HCV coinfection under antiretroviral therapy (ART) remains unexplored. This study aimed to identify specific patterns of CD39 expression on T-cells in ART-treated HIV/HCV coinfected patients and assess their relationship with systemic inflammation.
We conducted a case-control study that enrolled 41 HIV/HCV coinfected patients on stable ART (cases) and 23 healthy controls. CD39 expression on blood CD4 + and CD8 + T-cells, including CD45RA + and CD45RA – subsets, was quantified using flow cytometry. Cytokines were assessed using multiplex and enzyme-linked immunosorbent assays.
A significant proportion of CD4 + T-cells expressed CD39 in both groups (cases – 24.0%; controls – 16.1%). That was not true for CD8 + T-cells (cases – 3.2%; controls – 2.8%). CD39 expression was higher on CD45RA + than CD45RA – CD4 + T-cells (cases – 39.4% vs. 19.0%; controls – 24.6% vs. 9.2%). HIV/HCV coinfected patients exhibited a significantly increased proportion of CD39 + CD4 + T-cells compared to uninfected controls ( P < 0.01). A negative correlation was observed between the percentage of CD39 + CD4 + CD45RA – T-cells and levels of pro-inflammatory chemokines monocyte chemoattractant protein 1 (R = –0.392; P < 0.01) and eotaxin (R = –0.325; P < 0.05).
Thus, in this work, we have demonstrated that CD4 + T-cells, namely their CD45RA + subset, act as the main regulators of purinergic signals in HIV/HCV coinfected and healthy individuals. At the same time, the proportion of CD4 + T-cells involved in the control of purinergic signaling was increased in HIV/HCV coinfected patients compared with healthy subjects. These CD39-positive T-cells circulated between lymphoid organs and migrated to inflamed sites in response to increased concentrations of pro-inflammatory cytokines and chemokines.
At present, it remains unclear how effectively CD39-positive T-cells neutralize purinergic molecules. Moreover, our results raise a new question: how might a shift from effector to suppressor CD4 + T-cells affect the ability of the immune system to withstand newly emerging threats in HIV/HCV coinfected patients? Solving this and other questions requires further research.
https://www.xiahepublishing.com/1555-3884/GE-2025-00065
The study was recently published in the Gene Expression .
Gene Expression (GE) is an open-access journal. It was launched in 1991 by Chicago Medical School Press, and transferred to Cognizant Communication Corporation in 1994. From August 2022, GE is published by Xia & He Publishing Inc.
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Gene Expression
Specific Patterns of CD39 Expression on T-cells of HIV/HCV Coinfected Patients Receiving Antiretroviral Therapy: A Case-control Study
13-Jan-2026