LCMV induced downregulation of HVEM on antiviral T cells is critical for an efficient effector response. Issue 6 (18th April 2022)

• Record Type: Journal Article
• Authors: Diethelm, Patrizia; Schmitz, Iwana; Iten, Irina; Kisielow, Jan; Matsushita, Mai; Kopf, Manfred
• Is Part Of: European journal of immunology. Volume 52:Issue 6(2022)
• Page Start: 924
• Page End: 935
• Publication Date: 2022-04-18
• Subjects: HVEM -- BTLA -- T‐cell costimulation -- LCMV -- memory T cells; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.202048569
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: 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. Abstract : HVEM‐ligand interaction has been proposed to have differential effects on T‐cell response. Here, we investigate the role of HVEM upon acute and chronic lymphocytic choriomeningitis virus (LCMV) infection. We found that HVEM expression is potently downregulated during the effector phase in virus‐specific T cells and remained dampened even after in the memory phase (shown in red). Sustained HVEM expression by retroviral overexpression (in dashed blue lines) reduces the expansion of effector T cells, while resulting in increased memory T‐cell formation.