Age‐dependent changes in the sphingolipid composition of CD4+ T cell membranes and immune synapses

Abstract

Optimal T cell activation requires the formation of an immunological synapse (IS) and is driven by signaling ‘microclusters’ that associate with ordered membrane microdomains. Aging is associated with impaired IS formation and T cell activation. We hypothesized that age‐dependent changes in T cell lipid profiles impair IS formation and T cell activation in the aged. Total cell membrane (TCM) and IS fractions were prepared from the CD4+ T cells of young and old mice and subjected to ‘sphingolipidomic’ analysis. Both TCM and IS of aged CD4+ T cells have significantly higher levels of sphingomyelins and ceramides than young T cells. A subset of the lipids containing C14, C18:1, C26, and C26:1 fatty acid (FA) species was preferentially enriched in the IS. Young IS were enriched in C14 ceramide, C18:1 ceramide, C26:1 ceramide, and C14 hexosylceramide. Since sphingolipids are implicated in T cell activation and function, age‐dependent changes in the FA chain lengths and sphingolipid species retained in IS could influence T cell activation and function and may contribute to functional T cell defects in the aged.Supported by NIA R21‐AG030931, R01‐AG009140‐14, Office of Dietary Supplement, USDA‐ARS contract number 58‐1950‐7‐707, and LIPID MAPS Consortium.