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.
机构:
Heart Res Inst, Sydney, NSW 2042, Australia
Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, AustraliaHeart Res Inst, Sydney, NSW 2042, Australia
Tan, Joanne T. M.
Ng, Martin K. C.
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Heart Res Inst, Sydney, NSW 2042, Australia
Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia
Royal Prince Alfred Hosp, Dept Cardiol, Sydney, NSW, AustraliaHeart Res Inst, Sydney, NSW 2042, Australia
Ng, Martin K. C.
Bursill, Christina A.
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Heart Res Inst, Sydney, NSW 2042, Australia
Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, AustraliaHeart Res Inst, Sydney, NSW 2042, Australia
机构:
Chinese Acad Med Sci, Dept Pathol, Inst Basic Med Sci, Beijing 100005, Peoples R ChinaChinese Acad Med Sci, Dept Pathol, Inst Basic Med Sci, Beijing 100005, Peoples R China
She, MP
Wang, ZL
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机构:Chinese Acad Med Sci, Dept Pathol, Inst Basic Med Sci, Beijing 100005, Peoples R China
机构:
Univ Calif Los Angeles, Sch Med, Atherosclerosis Res Unit, Div Cardiol,Dept Med 47 123 CHS, Los Angeles, CA 90095 USAUniv Calif Los Angeles, Sch Med, Atherosclerosis Res Unit, Div Cardiol,Dept Med 47 123 CHS, Los Angeles, CA 90095 USA
Van Lenten, BJ
Navab, M
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机构:Univ Calif Los Angeles, Sch Med, Atherosclerosis Res Unit, Div Cardiol,Dept Med 47 123 CHS, Los Angeles, CA 90095 USA
Navab, M
Shih, D
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机构:Univ Calif Los Angeles, Sch Med, Atherosclerosis Res Unit, Div Cardiol,Dept Med 47 123 CHS, Los Angeles, CA 90095 USA
Shih, D
Fogelman, AM
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机构:Univ Calif Los Angeles, Sch Med, Atherosclerosis Res Unit, Div Cardiol,Dept Med 47 123 CHS, Los Angeles, CA 90095 USA
Fogelman, AM
Lusis, AJ
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机构:Univ Calif Los Angeles, Sch Med, Atherosclerosis Res Unit, Div Cardiol,Dept Med 47 123 CHS, Los Angeles, CA 90095 USA