title: Immunomodulatory role of high-density lipoproteins: impact on immunosenescence.
abstract: Natural aging is accompanied by a dysregulation of the host immune response that has well-known clinical consequences but poorly defined underlying causes. It has previously been reported that advancing age is associated with an increase in membrane cholesterol level in T cells. The aim of this study was to investigate whether high-density lipoprotein (HDL) can modulate the age-related accumulation of membrane cholesterol in T cells and impact on their subsequent responsiveness. Our data reveal that cholesterol metabolism, influx, and efflux are altered in T cells with aging, which may in part explain the increase in membrane cholesterol level observed in T cells in elderly individuals. HDL was unable to promote reverse cholesterol transport in T cells from elderly subjects with the same efficiency as was observed in T cells from young subjects besides unchanged ABCA-1 and SR-BI expressions. HDL exhibited a short-acting co-stimulatory effect by enhancing T cell production of interleukin-2 (IL-2). Moreover, HDL from healthy normolipemic individuals exerted differential effects on T cell proliferation that depended on the age of the HDL donor. Finally, HDL modulated TCR/CD28 activation by inducing sustained signaling through pLck, pERK, and pAkt. These data suggest that HDL has immunomodulatory effects on T cells that are influenced by age.
authors.affiliation: Singapore Immunology Network (SIgN), Biopolis, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore, Anis_Larbi@immunol.a-star.edu.sg.
authors.forename: Anis
authors.initials: A
authors.lastname: Larbi
authors.forename: Carl
authors.initials: C
authors.lastname: Fortin
authors.forename: Gilles
authors.initials: G
authors.lastname: Dupuis
authors.forename: Hicham
authors.initials: H
authors.lastname: Berrougui
authors.forename: Abdelouahed
authors.initials: A
authors.lastname: Khalil
authors.forename: Tamas
authors.initials: T
authors.lastname: Fulop
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology* / Q000378:metabolism; D001692:Biological Transport; D015153:Blotting, Western; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D056747:Immunomodulation / Q000502:physiology*; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D010641:Phenotype; D011971:Receptors, Immunologic / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D008075:Lipoproteins, HDL; D011971:Receptors, Immunologic