Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging.
Lipid rafts are critical to the assembly of the T-cell receptor (TCR) signaling machinery. It is not known whether lipid raft properties differ in CD4+ and CD8+ T cells and whether there are age-related differences that may account in part for immune senescence. Data presented here showed that time-dependent interleukin-2 (IL-2) production was different between CD4+ and CD8+ T cells. The defect in IL-2 production by CD4+ T cells was not due to lower levels of expression of the TCR or CD28. There was a direct correlation between the activation of p56(Lck) and LAT and their association/recruitment with the lipid raft fractions of CD4+ and CD8+ T cells. p56Lck, LAT and Akt/PKB were weakly phosphorylated in lipid rafts of stimulated CD4+ T cells of elderly as compared to young donors. Lipid rafts undergo changes in their lipid composition (ganglioside M1, cholesterol) in CD4+ and CD8+ T cells of elderly individuals. This study emphasizes the differential role of lipid rafts in CD4+ and CD8+ T-cell activation in aging and suggests that the differential localization of CD28 may explain disparities in response to stimulation in human aging.
Larbi
Anis
A
Research Center on Aging, 1036 Belvedere Street South, Sherbrooke, Quebec, Canada.
Dupuis
Gilles
G
Khalil
Abdelouahed
A
Douziech
Nadine
N
Fortin
Carl
C
Fülöp
Tamàs
T
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism; D004789:Enzyme Activation; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D021962:Membrane Microdomains / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens; D005732:Gangliosides; D007376:Interleukin-2; C110810:LAT protein, human; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D002784:Cholesterol; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051058:Oncogene Protein v-akt