Dietary fish oil diminishes the antigen presentation activity of rat dendritic cells.

The primary function of dendritic cells (DC) is the capture and processing of antigen and its presentation to T lymphocytes [l]. Indeed, it is now apparent that DC are the principal cell type able to stimulate T lymphocytes in v i m and in vivo. DC are required for antigen-specific T-cell proliferative responses, for T-celldependent antibody responses, for the development of cytotoxic T lymphocytes and for the proliferative response in the allogeneic mixed leukocyte reaction, they stimulate the syngeneic mixed leukocyte reaction and they are potent accessory cells for the polyclonal responses to mitogens [ 11. A requirement for antigenpresenting cell function is the expression of major histocompatibility complex class (MHC) I1 antigens on the cell surface. The T-cell proliferative response is related to the number of MHC II molecules on the surface of antigen-presenting cells; indeed the percentage of MHC 11-positive cells and the density of these molecules on the cell surface can alter the degree of immune responsiveness of an individual [2]. In addition to the requirement for MHC I1 expression, cell-cell adhesion is critical for initiation of a primary immune response. The importance of adhesion molecules such as CDl l a (leukocyte function associated molecule 1; LFA-1) and CD54 (intercellular adhesion molecule-1; ICAM-1) in the process of T-cell activation is demonstrated by the ability of monoclonal antibodies against these molecules to inhibit the T-cell proliferative response to mitogens and antigens in v im [3]. In recent years there has been great interest in the effects of different types of dietary fatty acids upon the immune system [see 4-6 for reviews]. Much of this interest has focused on the effects of the n-3 polyunsaturated fatty acids (PUFAs) found in fish oil (FO), which appear to have very potent actions in v i m and in vivo [see 4-6 for reviews]. There have been no reported studies of the effects of dietary lipids upon DC function. Since these cells are key antigen processing and presenting cells in vivo we considered it important to investigate the effect of dietary n-6 and n-3 PUFAs upon their ability to function and upon the surface expression of molecules involved in this function. Rats used were specific pathogen-free PVG-RT 1 C strain and were bred and housed in the MRC Cellular Immunology Unit, Sir William Dunn School of Pathology. They were subjected to mesenteric lymphadenectomy and then fed for six weeks on one of three diets (six animals per diet). These were a low fat (LF) diet which contained 2.5% by weight of corn oil and two high fat diets which contained either 20% by weight safflower oil (SO) or 20% by weight FO. SO is rich in the n-6 PUFA linoleic acid and FO is rich in the n-3 PUFAs, eicosapentaenoic and docosahexaenoic acids. Lymph-borne dendritic cells (L-DC) were obtained by purification of the cell preparation obtained by thoracic duct cannulation. Flow cytometry was used to determine the expression of markers (CD2, CDI la, CD18, CD40, CD54, MHC 11) on the surface of LDC. Prior to their use in the antigen presentation assay L-DC were pulsed for 2 h with antigen (keyhole limpet haemocyanin; KLH). The pulsed cells were washed and diluted to give 105, 5 x lo4 and lo4 L-DC/ml. They were then irradiated (2000 Rads, 30 min) on ice. Antigen presentation assays were performed in 96-