Extracellular vesicles in COVID-19 convalescence can regulate T cell metabolism and function, 2023, George et al.

[SNT Gatchaman]

Extracellular vesicles in COVID-19 convalescence can regulate T cell metabolism and function
Molly S. George; Jenifer Sanchez; Christina Rollings; David Fear; Peter Irving; Linda V. Sinclair; Anna Schurich

Long-term T cell dysregulation has been reported following COVID-19 disease. Prolonged T cell activation is associated with disease severity and may be implicated in producing long-covid symptoms. Here, we assess the role of extracellular vesicles (EV) in regulating T cell function over several weeks post COVID-19 disease. We find that alterations in cellular origin and protein content of EV in COVID-19 convalescence are linked to initial disease severity.

We demonstrate that convalescent donor-derived EV can alter the function and metabolic rewiring of CD4 and CD8 T cells. Of note, EV following mild, but not severe disease, show distinctly immune-suppressive properties, reducing T cell effector cytokine production and glucose metabolism. Mechanistically our data indicate the involvement of EV-surface ICAM-1 in facilitating EV—T cell interaction. Our data demonstrate that circulatory EV are phenotypically and functionally altered several weeks following acute infection, suggesting a role for EV as long-term immune modulators.

Link | PDF (iScience)

 

[SNT Gatchaman]

The most striking impact on T cells was mediated by EV isolated from mild COVID-19 convalescent donors; these EV significantly suppressed IFNg and TNFa effector cytokine production in both CD4 and CD8 T cells as well as inducing metabolic modulation; specifically, nutrient transporter downregulation and mitochondrial dysfunction.

Also noting —

T cells treated with EV derived from vaccinated donors also showed reduced protein synthesis

Taken together, our data demonstrate that infection with SARS-CoV-2 has long-term impacts on the profile of circulating EV, with EV surface and intra-vesicle protein content linked to initial disease severity. We provide evidence that EV can modulate T cell responses several weeks post COVID-19 disease, impacting T cell activation, metabolic profile, and effector functions. Specifically following mild infection, EV are suppressive to T cell function.

Which might have implications for herpesvirus reactivation, eg EBV. From Epstein–Barr virus and multiple sclerosis (2022, Nature Reviews Microbiology) —

Most individuals maintain lifelong, effective immune control of the virus, where reactivation occasionally occurs but is quickly suppressed. This effective immune control is dominated by CD8 + T cells that target latently infected cells and early lytic replication

T cell control of EBV infection is required for homeostatic viral persistence, and immune dysregulation is observed in all EBV-associated disease. In healthy carriers of latent EBV infection (more than 90% of the adult population), nearly 1% of all T cells are reactive to EBV latent or lytic antigens