LCMV induced downregulation of HVEM on antiviral T cells is critical for an efficient effector response.
Patrizia DiethelmIwana SchmitzIrina ItenJan KisielowMai MatsushitaManfred KopfPublished in: European journal of immunology (2022)
T-cell responses against tumors and pathogens are critically shaped by cosignaling molecules providing a second signal. Interaction of herpes virus entry mediator (HVEM, CD270, TNFRSF14) with multiple ligands has been proposed to promote or inhibit T-cell responses and inflammation, dependent on the context. In this study, we show that absence of HVEM did neither affect generation of effector nor maintenance of memory antiviral T cells and accordingly viral clearance upon acute and chronic lymphocytic choriomeningitis virus (LCMV) infection, due to potent HVEM downregulation during infection. Notably, overexpression of HVEM on virus-specific CD8 + T cells resulted in a reduction of effector cells, whereas numbers of memory cells were increased. Overall, this study indicates that downregulation of HVEM driven by LCMV infection ensures an efficient acute response at the price of impaired formation of T-cell memory.
Keyphrases
- induced apoptosis
- cell proliferation
- signaling pathway
- liver failure
- regulatory t cells
- drug induced
- dendritic cells
- working memory
- cell cycle arrest
- oxidative stress
- sars cov
- respiratory failure
- type iii
- immune response
- intensive care unit
- cell death
- hepatitis b virus
- diabetic rats
- endoplasmic reticulum stress
- high glucose
- gram negative
- antimicrobial resistance
- stress induced