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Title: Cytomegalovirus restricts ICOSL expression on antigen-presenting cells disabling T cell co-stimulation and contributing to immune evasion
Author: Angulo, Guillem
Zeleznjak, Jelena
Martínez Vicente, Pablo
Puñet Ortiz, Joan
Hengel, Hartmut
Messerle, Martin
Oxenius, Annette
Jonjic, Stipan
Krmpotić, Astrid
Engel Rocamora, Pablo
Angulo Aguado, Ana
Keywords: Antígens
Immunitat cel·lular
Cèl·lules T
Malalties víriques
Ratolins (Animals de laboratori)
Cellular immunity
T cells
Virus diseases
Mice (Laboratory animals)
Issue Date: 18-Jan-2021
Publisher: eLife Sciences
Abstract: Viral infections are controlled, and very often cleared, by activated T lymphocytes. The inducible co-stimulator (ICOS) mediates its functions by binding to its ligand ICOSL, enhancing T-cell activation and optimal germinal center (GC) formation. Here, we show that ICOSL is heavily downmodulated during infection of antigen-presenting cells by different herpesviruses. We found that, in murine cytomegalovirus (MCMV), the immunoevasin m138/fcr-1 physically interacts with ICOSL, impeding its maturation and promoting its lysosomal degradation. This viral protein counteracts T-cell responses, in an ICOS-dependent manner, and limits virus control during the acute MCMV infection. Additionally, we report that blockade of ICOSL in MCMV-infected mice critically regulates the production of MCMV-specific antibodies due to a reduction of T follicular helper and GC B cells. Altogether, these findings reveal a novel mechanism evolved by MCMV to counteract adaptive immune surveillance, and demonstrates a role of the ICOS:ICOSL axis in the host defense against herpesviruses.
Note: Reproducció del document publicat a:
It is part of: eLife, 2021, vol. 10, num. e59350
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ISSN: 2050-084X
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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