title: CD4(+) T-cell activation is differentially modulated by bacteria-primed dendritic cells, but is generally down-regulated by n-3 polyunsaturated fatty acids.
abstract: Appropriate activation of CD4(+) T cells is fundamental for efficient initiation and progression of acquired immune responses. Here, we showed that CD4(+) T-cell activation is dependent on changes in membrane n-3 polyunsaturated fatty acids (PUFAs) and is dynamically regulated by the type of signals provided by dendritic cells (DCs). Upon interaction with DCs primed by different concentrations and species of gut bacteria, CD4(+) T cells were activated according to the type of DC stimulus. The levels of CD80 were found to correlate to the levels of expression of CD28 and to the proliferation of CD4(+) T cells, while the presence of CD40 and CD86 on DCs inversely affected inducible costimulator (ICOS) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in CD4(+) T cells. For all DC stimuli, cells high in n-3 PUFAs showed reduced ability to respond to CD28 stimulation, to proliferate, and to express ICOS and CTLA-4. Diminished T-cell receptor (TCR) and CD28 signalling was found to be responsible for n-3 PUFA effects. Thus, the dietary fatty acid composition influences the overall level of CD4(+) T-cell activation induced by DCs, while the priming effect of the DC stimuli modulates CD80, CD86 and CD40 levels, thereby affecting and shaping activation of acquired immunity by differential regulation of proliferation and costimulatory molecule expression in CD4(+) T cells.
authors.affiliation: Nutritional Immunology Group, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark. sbp@bio.dtu.dk
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
authors.forename: Pia
authors.initials: P
authors.lastname: Lund
authors.forename: Tanja M R
authors.initials: TM
authors.lastname: Kjaer
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Straarup
authors.forename: Lars I
authors.initials: LI
authors.lastname: Hellgren
authors.forename: Hanne
authors.initials: H
authors.lastname: Frøkiaer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000276:immunology; D001419:Bacteria / Q000276:immunology*; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D060908:CTLA-4 Antigen; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004041:Dietary Fats / Q000276:immunology / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000502:physiology*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008643:Mesentery / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D004041:Dietary Fats; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D000949:Histocompatibility Antigens Class II; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; D008070:Lipopolysaccharides; D016753:Interleukin-10; D007371:Interferon-gamma