title: CD40 is necessary for activation of naïve T cells by a dendritic cell line in vivo but not in vitro.
abstract: The importance of CD40-CD40L interactions during CD4(+) T-cell activation has been extensively investigated over the years; however, it still remains questionable whether the interaction is a prerequisite for dendritic cell (DC)-mediated antigen-specific priming in vivo. Naïve CD4(+) T cells require two signals for proper activation and induction of differentiation: signal 1 is provided by peptide antigens in the context of the major histocompatibility complex (MHC) class II, while signal 2 is delivered by costimulatory molecules such as CD80 or CD86 present on the antigen-presenting cell (APC). It is well known that the expression of CD80/CD86 is upregulated after interaction between CD40 on APCs and CD40L expressed by at least partly activated T cells. We used a DC line, JawsII, to compare the importance of CD40 expression and downstream signalling in vitro and in vivo. JawsII cells represent pre-immature bone marrow-derived DCs expressing low levels of MHC molecules, low levels of B7 molecules and no CD40. We have previously shown that JawsII cells, despite the lack of CD40 expression, are capable of priming naïve allogeneic T cells in vitro. In correlation with the current literature, we present data showing that constitutive expression of CD40 significantly increases the priming capacity of JawsII cells in vitro. In addition, we show that CD40 expression is required for JawsII cell-dependent T-cell priming in vivo.
authors.affiliation: Hagedorn Research Institute, Gentofte, Denmark. csha@novonordisk.com
authors.forename: C
authors.initials: C
authors.lastname: Haase
authors.forename: B K
authors.initials: BK
authors.lastname: Michelsen
authors.forename: T N
authors.initials: TN
authors.lastname: Jørgensen
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014161:Transduction, Genetic
chemical_list: D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D012313:RNA