Linking innate and acquired immunity: divergent role of CD46 cytoplasmic domains in T cell–induced inflammation

Abstract

CD46 is a widely expressed transmembrane protein that was initially identified as binding and inactivating C3b and C4b complement products. We used mice that were transgenic for one of two human CD46 isoforms that differ in their cytoplasmic domains (termed CD46-1 and CD46-2) to analyze the effect of CD46 stimulation on the immune response. We show here that CD46 can regulate inflammatory responses, either by inhibiting (CD46-1) or increasing (CD46-2) the contact hypersensitivity reaction. We found that engagement of CD46-1 or CD46-2 differentially affected CD8(+) T cell cytotoxicity, CD4(+) T cell proliferation, interleukin 2 (IL-2) and IL-10 production as well as tyrosine phosphorylation of Vav in T lymphocytes. These results indicate that CD46 plays a role in regulating the T cell induced inflammatory reaction and in fine-tuning the cellular immune response by bridging innate and acquired immunity.

Measles virus hemagglutinin triggers intracellular signaling in CD150-expressing dendritic cells and inhibits immune response

“…About 8-to 12-week-old CD150tg mice or C57Bl/6 mice (Charles River, France) were injected i.p. with mock preparation, VSV or VSV-H UV-irradiated viruses at 5 3 10 6 PFU, and contact hypersensitivity to dinitrofluorobenzene (DNFB) was assayed as described 32 . The protocol was approved by the Regional Animal Care Committee (CREEA).…”

“…CD150 was engaged by injecting UV-inactivated vesicular stomatitis virus (UV-VSV), expressing or not MV-H 28 . This approach has already been shown to stimulate efficiently immune cell membrane receptors in transgenic mice in vivo 32 .…”

Des séquences rétrovirales endogènes dans le génome humain peuvent jouer un rôle physiologique ou pathologique

“…Cette transactivation étant quasi immédiate après l'entrée d'EBV dans les cellules, il n'est pas nécessaire qu'il y ait une réplication virale. De même, la transcription du superantigène HERV-K18 serait induite par l'interaction de la glycoprotéine H de l'herpèsvirus HHV-6B avec le CD46 [18], un récepteur ubiquitaire des fragments C3b et C4b du complément, un dimère immunorégulateur dont la queue cytoplasmique est contituée des sous-unités Cyt1 ou Cyt2, respectivement anti-et pro-inflammatoire [19]. La modulation de la réponse innée pourrait donc influer sur l'état d'activité des séquences HERV-K.…”

Transduction of Liver Metastases After Intravenous Injection of Ad5/35 or Ad35 Vectors With and Without Factor X-Binding Protein Pretreatment

“…All mice were housed in specific pathogen-free facilities. The CD46 transgenic C57BL=6 mouse line MCP8B (C57-CD46) was generously provided by B. Horvat (INSERM, Paris, France) (Marie et al, 2002). (This line has been crossed into the C57BL=6 background for nine generations.)…”