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A more recent version of this article appeared on February 1, 2004

Published online before print December 4, 2003
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0703319


Received for publication July 9, 2003.
Revised September 19, 2003.
Accepted for publication October 6, 2003.


Article

Age-associated alterations in the recruitment of signal-transduction proteins to lipid rafts in human T lymphocytes

Anis Larbi *{dagger}, Nadine Douziech *, Gilles Dupuis {dagger}{ddagger}, Abdelouahed Khalil *, Hugues Pelletier *, Karl-Philippe Guerard *, and Tamàs Fülöp Jr.*{dagger}§@

*Research Center on Aging, Geriatric Institute, {dagger}Graduate Program in Immunology, Clinical Research Center, and Departments of {ddagger}Biochemistry, Faculty of Medicine, and §Medicine, Geriatric Division, University of Sherbrooke, Quebec, Canada

@ To whom correspondence should be addressed. E-mail: tamas.fulop{at}usherbrooke.ca.


   Abstract

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 p56lck, 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.

Key Words: T cell receptor • LAT • p56Lck • aging • cholesterol




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