Age-associated alterations in the recruitment of signal-transduction proteins to lipid rafts in human T lymphocytes.
Aging is associated with a decline in T cell activation and proliferation, but the underlying mechanisms are not fully understood. Recent findings suggest that lipid rafts act as a platform in the initiation of T cell activation by selectively recruiting signaling proteins associated with formation of the initial complex of signal transduction. We tested the hypothesis that lipid raft properties are altered in T lymphocytes from elderly, healthy individuals in comparison with young subjects. Results showed that the cholesterol content of lipid rafts derived from these cells was consistently higher in the case of elderly donors and that membrane fluidity was decreased. In addition, lipid rafts coalescence to the site of T cell receptor engagement was impaired in T cells from elderly donors. The recruitment of p56(lck), linker of activated T cells, and their tyrosine-phosphorylated forms to lipid rafts was decreased in activated T cells from aged individuals. CD45 was not recruited to the lipid raft fractions in either group of subjects. Our data suggest that some properties of lipid rafts are altered in aging, and this finding may be part of the causes for the decline in T cell functions that are observed in elderly individuals.
Larbi
Anis
A
Research Center on Aging, Geriatric Institute, Clinical Research Center, University of Sherbrooke, 1036 Belvedere St. South, Sherbrooke, QC, Canada J1H 4C4.
Douziech
Nadine
N
Dupuis
Gilles
G
Khalil
Abdelouahed
A
Pelletier
Hugues
H
Guerard
Karl-Philippe
KP
Fülöp
Tamàs
T
D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D002784:Cholesterol / Q000032:analysis; D005260:Female; D006801:Humans; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008297:Male; D008560:Membrane Fluidity; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D002784:Cholesterol; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D017493:Leukocyte Common Antigens