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

被引:86
作者
Larbi, A
Douziech, N
Dupuis, G
Khalil, A
Pelletier, H
Guerard, KP
Fulop, T
机构
[1] Univ Sherbrooke, Res Ctr Aging, Geriatr Inst, Sherbrooke, PQ J1H 4C4, Canada
[2] Univ Sherbrooke, Clin Res Ctr, Grad Program Immunol, Sherbrooke, PQ J1H 4C4, Canada
[3] Univ Sherbrooke, Dept Biochem, Fac Med, Sherbrooke, PQ J1H 4C4, Canada
[4] Univ Sherbrooke, Dept Med, Div Geriatr, Sherbrooke, PQ J1H 4C4, Canada
关键词
T cell receptor; LAT; p56(Lck); aging; cholesterol;
D O I
10.1189/jlb.0703319
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 ceIls, and their tyrosine-phosphorylated forms to lipid rafts was decreased in activated T ceIls 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.
引用
收藏
页码:373 / 381
页数:9
相关论文
共 64 条
[1]  
Alonso MA, 2001, J CELL SCI, V114, P3957
[2]  
Beck R, 1998, CIRC RES, V83, P923
[3]  
Ben-Yehuda A, 1992, Clin Geriatr Med, V8, P701
[4]   Antigen-induced translocation of PKC-θ to membrane rafts is required for T cell activation [J].
Bi, K ;
Tanaka, Y ;
Coudronniere, N ;
Sugie, K ;
Hong, SJ ;
van Stipdonk, MJB ;
Altman, A .
NATURE IMMUNOLOGY, 2001, 2 (06) :556-563
[5]   ITAMs versus ITIMs: striking a balance during cell regulation [J].
Billadeau, DD ;
Leibson, PJ .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 109 (02) :161-168
[6]   Extensive temporally regulated reorganization of the lipid raft proteome following T-cell antigen receptor triggering [J].
Bini, L ;
Pacini, S ;
Liberatori, S ;
Valensin, S ;
Pellegrini, M ;
Raggiaschi, R ;
Pallini, V ;
Baldari, CT .
BIOCHEMICAL JOURNAL, 2003, 369 :301-309
[7]   Association of the adaptor molecule LAT with CD4 and CD8 coreceptors identifies a new coreceptor function in T cell receptor signal transduction [J].
Bosselut, R ;
Zhang, WG ;
Ashe, JM ;
Kopacz, JL ;
Samelson, LE ;
Singer, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 190 (10) :1517-1525
[8]   CD28 expression in T cell aging and human longevity [J].
Boucher, N ;
Dufeu-Duchesne, T ;
Vicaut, E ;
Farge, D ;
Effros, RB ;
Schachter, F .
EXPERIMENTAL GERONTOLOGY, 1998, 33 (03) :267-282
[9]   Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells [J].
Brenchley, JM ;
Karandikar, NJ ;
Betts, MR ;
Ambrozak, DR ;
Hill, BJ ;
Crotty, LE ;
Casazza, JP ;
Kuruppu, J ;
Migueles, SA ;
Connors, M ;
Roederer, M ;
Douek, DC ;
Koup, RA .
BLOOD, 2003, 101 (07) :2711-2720
[10]   Quantitative imaging of raft accumulation in the immunological synapse [J].
Burack, WR ;
Lee, KH ;
Holdorf, AD ;
Dustin, ML ;
Shaw, AS .
JOURNAL OF IMMUNOLOGY, 2002, 169 (06) :2837-2841