title: MHC class II expression through a hitherto unknown pathway supports T helper cell-dependent immune responses: implications for MHC class II deficiency.
abstract: MHC class II (MHCII) deficiency or bare lymphocyte syndrome (BLS) is a severe immunodeficiency characterized by deficient T helper (Th)-cell-dependent immunity. The disease is caused by defects of the MHCII promoter complex resulting in low or absent MHCII expression. We demonstrate in a murine model of MHCII deficiency (RFX5- or CIITA-deficient mice) that residual MHCII expression by professional antigen-presenting cells (APCs) is sufficient to support activation of adoptively transferred Th cells. Furthermore, upon transplantation of WT thymic epithelium, we observed development of endogenous Th cells with restoration of Th-cell-dependent antibody responses and immunity to cytomegalovirus infection, thus opening the possibility of an alternative treatment regimen for BLS. Residual MHCII expression was further induced by the presence of Th cells and also other stimuli. Analysis of CIITA/RFX5 double-deficient animals revealed that this inducible MHCII expression is genetically independent of the known promoter complex and thus constitutes an alternative MHCII expression pathway. In these experiments, we also detected a novel repressive function of the RFX complex in the absence of CIITA.
authors.affiliation: Institut für Umweltmedizinische Forschung gGmbH, Heinrich-Heine University, Auf'm Hennekamp 50, D-40225 Düsseldorf, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Buch
authors.forename: Bojan
authors.initials: B
authors.lastname: Polic
authors.forename: Björn E
authors.initials: BE
authors.lastname: Clausen
authors.forename: Susanne
authors.initials: S
authors.lastname: Weiss
authors.forename: Ozlem
authors.initials: O
authors.lastname: Akilli-Ozturk
authors.forename: Cheong-Hee
authors.initials: CH
authors.lastname: Chang
authors.forename: Richard
authors.initials: R
authors.lastname: Flavell
authors.forename: Ansgar
authors.initials: A
authors.lastname: Schulz
authors.forename: Stipan
authors.initials: S
authors.lastname: Jonjic
authors.forename: Ari
authors.initials: A
authors.lastname: Waisman
authors.forename: Irmgard
authors.initials: I
authors.lastname: Förster
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D007109:Immunity; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; C509133:RFX5 protein, mouse; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors