Although it is recognized that lipids and membrane organization in T cells affect signaling and T cell activation, to what extent dietary lipids alter T cell responsiveness in the absence of obesity and inflammation is not known. In this study, we fed low-density lipoprotein receptor knockout mice a Western high-fat diet for 1 or 9 wk and examined T cell responses in vivo along with T cell lipid composition, membrane order, and activation ex vivo. Our data showed that high levels of circulating lipids for a prolonged period elevated CD4+ and CD8+ T cell proliferation and resulted in an increased proportion of CD4+ central-memory T cells within the draining lymph nodes following induction of contact hypersensitivity. In addition, the 9-wk Western high-fat diet elevated the total phospholipid content and monounsaturated fatty acid level, but decreased saturated phosphatidylcholine and sphingomyelin within the T cells. The altered lipid composition in the circulation, and of T cells, was also reflected by enhanced membrane order at the activation site of ex vivo activated T cells that corresponded to increased IL-2 mRNA levels. In conclusion, dietary lipids can modulate T cell lipid composition and responses in lipoprotein receptor knockout mice even in the absence of excess weight gain and a proinflammatory environment.
This work was supported by National Health and Medical Research Council of Australia Grants 1022182 (to K.G. and J.R.), 1037320 (to R.G.P. and K.G.), and1059278 (to K.G.), and by Australian Research Council Grant CE140100011 (to K.G.).
The online version of this article contains supplemental material.
Abbreviations used in this article:
- contact hypersensitivity
- generalized polarization
- low density lipoprotein receptor knockout
- phosphatidic acid
- proliferating cell nuclear Ag
- Western high-fat
- Received June 11, 2015.
- Accepted March 13, 2016.
- Copyright © 2016 by The American Association of Immunologists, Inc.