Dietary n-3 PUFA affect TcR-mediated activation of purified murine T cells and accessory cell function in co-cultures.
Diets enriched in n-3 polyunsaturated fatty acids (PUFA) suppress several functions of murine splenic T cells by acting directly on the T cells and/or indirectly on accessory cells. In this study, the relative contribution of highly purified populations of the two cell types to the dietary suppression of T cell function was examined. Mice were fed diets containing different levels of n-3 PUFA; safflower oil (SAF; control containing no n-3 PUFA), fish oil (FO) at 2% and 4%, or 1% purified docosahexaenoic acid (DHA) for 2 weeks. Purified (>90%) T cells were obtained from the spleen, and accessory cells (>95% adherent, esterase-positive) were obtained by peritoneal lavage. Purified T cells or accessory cells from each diet group were co-cultured with the alternative cell type from every other diet group, yielding a total of 16 different co-culture combinations. The T cells were stimulated with either concanavalin A (ConA) or antibodies to the T cell receptor (TcR)/CD3 complex and the costimulatory molecule CD28 (alphaCD3/alphaCD28), and proliferation was measured after four days. Suppression of T cell proliferation in the co-cultures was dependent upon the dose of dietary n-3 PUFA fed to mice from which the T cells were derived, irrespective of the dietary treatment of accessory cell donors. The greatest dietary effect was seen in mice consuming the DHA diet (P = 0.034 in the anova; P=0.0053 in the Trend Test), and was observed with direct stimulation of the T cell receptor and CD28 costimulatory ligand, but not with ConA. A significant dietary effect was also contributed accessory cells (P = 0.033 in the Trend Test). We conclude that dietary n-3 PUFA affect TcR-mediated by T cell activation by both direct and indirect (accessory cell) mechanisms.
Chapkin
R S
RS
Faculty of Nutrition, Center for Environmental and Rural, Health and Department of Statistics, Texas 77843-1114, USA.
Arrington
J L
JL
Apanasovich
T V
TV
Carroll
R J
RJ
McMurray
D N
DN
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects* / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D018920:Coculture Techniques; D003208:Concanavalin A / Q000494:pharmacology; D004041:Dietary Fats / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D005395:Fish Oils / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012450:Safflower Oil / Q000494:pharmacology; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology
D018106:CD28 Antigens; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007166:Immunosuppressive Agents; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003208:Concanavalin A; D004281:Docosahexaenoic Acids; D012450:Safflower Oil