Inversed Ratio of CD39/CD73 Expression on γδ T Cells in HIV Versus Healthy Controls Correlates With Immune Activation and Disease Progression

Abstract

Backgroundγδ T cells are unconventional T cells that have been demonstrated to be crucial for the pathogenesis and potentially for the cure of HIV-1 infection. The ectonucleotidase CD39 is part of the purinergic pathway that regulates immune responses by degradation of pro-inflammatory ATP in concert with CD73. Few studies on the expression of the ectoenzymes CD73 and CD39 on human γδ T cells in HIV have been performed to date.MethodsPBMC of n=86 HIV-1-infected patients were compared to PBMC of n=26 healthy individuals using 16-color flow cytometry determining the surface expression of CD39 and CD73 on Vδ1 and Vδ2 T cells in association with differentiation (CD45RA, CD28, CD27), activation and exhaustion (TIGIT, PD-1, CD38, and HLA-DR), and assessing the intracellular production of pro- and anti-inflammatory cytokines (IL-2, TGF-ß, TNF-α, Granzyme B, IL-10, IFN-γ) after in vitro stimulation with PMA/ionomycin.ResultsCD39 and CD73 expression on γδ T cells were inversed in HIV infection which correlated with HIV disease progression and immune activation. CD39, but not CD73 expression on γδ T cells of ART-treated patients returned to levels comparable with those of healthy individuals. Only a small subset (<1%) of γδ T cells co-expressed CD39 and CD73 in healthy or HIV-infected individuals. There were significantly more exhausted and terminally differentiated CD39+ Vδ1 T cells regardless of the disease status. Functionally, IL-10 was only detectable in CD39+ γδ T cells after in vitro stimulation in all groups studied. Viremic HIV-infected patients showed the highest levels of IL-10 production. The highest percentage of IL-10+ cells was found in the small CD39/CD73 co-expressing γδ T-cell population, both in healthy and HIV-infected individuals. Also, CD39+ Vδ2 T cells produced IL-10 more frequently than their CD39+ Vδ1 counterparts in all individuals regardless of the HIV status.ConclusionsOur results point towards a potential immunomodulatory role of CD39+ and CD73+ γδ T cells in the pathogenesis of chronic HIV infection that needs further investigation.

High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

“…Purinergic signaling is of increasing interest in many infectious diseases [51][52][53][54][55][56]. We investigated the expression of CD39 and CD73 on bulk and SARS-CoV-2-specific CD4 + T-cells.…”

“…Increasing evidence has been generated for the immunomodulatory functions of purinergic signaling in viral infections such as HIV and other infectious diseases [51][52][53][54][55][56]. During inflammation and tissue damage, adenosine triphosphate (ATP) is released to extracellular compartments, and acts as a pro-inflammatory mediator [57][58][59].…”

The Role of Cluster of Differentiation 39 (CD39) and Purinergic Signaling Pathway in Viral Infections

“…The frequency of CD39 on γδ T lymphocytes correlates with immune activation, CD4 count, and viral load. Moreover, CD39 and CD73 could identify the γδ T cells that secrete massive amounts of IL-10 [ 34 ].…”