| Literature DB >> 35657354 |
Benjamin Fournier1,2,3, Akihiro Hoshino1, Anne-Sophie Defachelles4, Bénédicte Neven2,3, Julie Bruneau5, Camille Bachelet1,2, Mathieu Fusaro1,2,6, Roman Klifa3, Romain Lévy3, Christelle Lenoir1, Claire Soudais1,2, Capucine Picard1,2,6, Stéphane Blanche3, Martin Castelle3, Despina Moshous2,3, Thierry Molina5, Sylvain Latour1,2.
Abstract
Epstein-Barr virus (EBV) can infect smooth muscle cells causing smooth muscle tumors (SMTs) or leiomyoma. Here, we report a patient with a heterozygous 22q11.2 deletion/DiGeorge syndrome who developed a unique, broad, and lethal susceptibility to EBV characterized by EBV-infected T and B cells and disseminated EBV+SMT. The patient also harbored a homozygous missense mutation (p.V140G) in TNFSF9 coding for CD137L/4-1BBL, the ligand of the T cell co-stimulatory molecule CD137/4-1BB, whose deficiency predisposes to EBV infection. We show that wild-type CD137L was up-regulated on activated monocytes and dendritic cells, EBV-infected B cells, and SMT. The CD137LV140G mutant was weakly expressed on patient cells or when ectopically expressed in HEK and P815 cells. Importantly, patient EBV-infected B cells failed to trigger the expansion of EBV-specific T cells, resulting in decreased T cell effector responses. T cell expansion was recovered when CD137L expression was restored on B cells. Therefore, these results highlight the critical role of the CD137-CD137L pathway in anti-EBV immunity, in particular in the control of EBV+SMT.Entities:
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Year: 2022 PMID： 35657354 PMCID： PMC9170382 DOI： 10.1084/jem.20211682
Source DB: PubMed Journal: J Exp Med ISSN： 0022-1007 Impact factor: 17.579