Study reveals immune changes in HIV and HCV coinfected patients

Background and objectives

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.

Methods

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.

Results

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).

Conclusions

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.