Fatty acid composition and metabolic partitioning of a-linolenic acid are contingent on life stage in human CD3+ T lymphocytes

Introduction: Immune function changes across the life course; the fetal immune system is characterised by tolerance while that of seniors is less able to respond effectively to antigens and is more pro-inflammatory than in younger adults. Lipids are involved centrally in immune function but there is limited information about how T cell lipid metabolism changes during the life course. Methods and Results: We investigated whether life stage alters fatty acid composition, lipid droplet content and alpha-linolenic acid (18:3 omega-3) metabolism in human fetal CD3(+) T lymphocytes and in CD3(+) T lymphocytes from adults (median 41 years) and seniors (median 70 years). Quiescent fetal T cells had higher saturated (SFA), monounsaturated fatty acid (MUFA), and omega-6 polyunsaturated fatty acid (PUFA) contents than adults or seniors. Activation-induced changes in fatty acid composition differed between life stages. The principal metabolic fates of [C-13]18:3 omega-3 were constitutive hydroxyoctadecatrienoic acid synthesis and beta-oxidation and carbon recycling into SFA and MUFA. These processes declined progressively across the life course. Longer chain omega-3 PUFA synthesis was a relatively minor metabolic fate of 18:3 omega-3 at all life stages. Fetal and adult T lymphocytes had similar lipid droplet contents, which were lower than in T cells from seniors. Variation in the lipid droplet content of adult T cells accounted for 62% of the variation in mitogen-induced CD69 expression, but there was no significant relationship in fetal cells or lymphocytes from seniors. Discussion: Together these findings show that fatty acid metabolism in human T lymphocytes changes across the life course in a manner that may facilitate the adaptation of immune function to different life stages.

Automated summary

This study found that lipid metabolism in human T lymphocytes changes during the life course, which may facilitate the adaptation of immune function to different stages of life.