title: A role for the transcription factor RelB in IFN-alpha production and in IFN-alpha-stimulated cross-priming.
abstract: Chimeric mice generated with bone marrow from RelB-deficient (-/-), RelB-heterozygous (+/-) and wild-type (+/+) mice were used to determine how total or partial absence of the transcription factor RelB in haematopoietic cells affects the immune response generated after lymphocytic choriomeningitis virus (LCMV) infection. In RelB(-/-) chimeras, early virus replication was enhanced and LCMV clearance was impaired. Although plasmacytoid dendritic cell numbers were similar, serum interferon (IFN)-alpha levels in RelB(-/-) and RelB(+/-) chimeras were markedly lower than in RelB(+/+) chimeras during early LCMV infection. Further, both RelB(-/-) and RelB(+/-) chimeras mounted a lower-magnitude LCMV-specific CD8(+) T cell response than their RelB(+/+) counterparts, although the LCMV-specific CD8(+) T cells present were differentiated into functional cytotoxic cells. In LCMV-infected RelB(-/-) mice, induction of cross-priming to an independently injected soluble protein, which depends on the IFN-alpha/beta made during the viral infection, was also impaired. Notably, provision of exogenous IFN-alpha did not restore the ability of RelB(-/-) mice to cross-prime. In summary, these results show that the RelB/NF-kappaB pathway is required for optimal IFN-alpha production after LCMV infection and suggest a crucial role for RelB in IFN-alpha-stimulated cross-priming of CD8(+) T cell responses.
authors.affiliation: The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire, UK.
authors.forename: Agne
authors.initials: A
authors.lastname: Le Bon
authors.forename: Maria
authors.initials: M
authors.lastname: Montoya
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Edwards
authors.forename: Clare
authors.initials: C
authors.lastname: Thompson
authors.forename: Shannon A
authors.initials: SA
authors.lastname: Burke
authors.forename: Miranda
authors.initials: M
authors.lastname: Ashton
authors.forename: David
authors.initials: D
authors.lastname: Lo
authors.forename: David F
authors.initials: DF
authors.lastname: Tough
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
mesh_terms: D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D002678:Chimera / Q000235:genetics; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D013154:Spleen / Q000002:abnormalities / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051841:Transcription Factor RelB / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D016898:Interferon-alpha; D051841:Transcription Factor RelB; D010047:Ovalbumin