Modulation of human lymphocyte proliferative response with aging

被引:76
作者
Douziech, N
Seres, L
Larbi, A
Szikszay, E
Roy, PM
Arcand, M
Dupuis, G
Fulop, T
机构
[1] Inst Univ Geriatrie Sherbrooke, Ctr Rech Gerontol & Geriatrie, Sherbrooke, PQ J1H 4C4, Canada
[2] Univ Debrecen, Med & Hlth Sci Ctr, Dept Med 1, H-4012 Debrecen, Hungary
[3] Univ Sherbrooke, Fac Med, Dept Biochim, Sherbrooke, PQ, Canada
关键词
T lymphocytes; aging; TcR/CD3; complex; signal transduction; proliferation; cyclodextrin; membrane rafts; vitamin E; vitamin C; mitogen-activated protein kinase;
D O I
10.1016/S0531-5565(01)00204-2
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Previously, we have demonstrated age-associated alterations in transmembrane signaling. One of the most reproducible alterations found in the immune response with aging is the decrease of lymphocyte proliferation on stimulation with various different mitogens. Here, we confirm that proliferative responses to stimulation with phytohaemagglutin (PHA), recombinant human IL-2, or anti-CD3 monoclonal antibody are all greater in the young (20-25 years) than old (60-87 years) population. We attempted to modulate the proliferative response using various agents acting at different levels of transmembrane signaling (pertussis toxin, cholera toxin, isoproterenol, PMA, Ca ionophore A23187), as well as at the level of the lymphocyte plasma membrane (methyl-p-cyclodextrin, MBCD), or by using antioxidant vitamins (Vitamin E or Q. None of these agents was able to restore effectively the proliferative response of lymphocytes from the aged to the level of young subjects. Even the combination of A23187 and PMA acting directly on calcium metabolism and protein kinase C activity was insufficient to restore the decreased mitogenic capacity of T cells from elderly subjects. Cyclodextrin, which decreases the cholesterol content of the membrane, increased the proliferative response of lymphocytes of elderly subjects, but not to the level of the young. Vitamin E had a very strong inhibitory effect on lymphocyte stimulation in both the age groups, except in combination with MBCD in T cells of the elderly, while Vitamin C had no significant modulatory effect. MAPK ERK and p38 activation was found to be decreased with aging in T cells after anti-CD3 mAb stimulation. Vitamin E but not Vitamin C strongly inhibited MAPK ERK or p38 activation. The direct activation of certain molecules or the modulation of the cholesterol content of the membrane seems to be effective immunomodulatory interventions with aging. (C) 2002 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:369 / 387
页数:19
相关论文
共 108 条
[1]  
Ahnadi CE, 2000, J LEUKOCYTE BIOL, V68, P293
[2]   COSTIMULATORY SIGNALS MODULATE THE ANTIPROLIFERATIVE EFFECTS OF AGENTS THAT ELEVATE CAMP IN T-CELLS [J].
BARTIK, MM ;
BAUMAN, GP ;
BROOKS, WH ;
ROSZMAN, TL .
CELLULAR IMMUNOLOGY, 1994, 158 (01) :116-130
[3]   INDUCTION OF CAMP-DEPENDENT PROTEIN-KINASE (PKA) ACTIVITY IN T-CELLS AFTER STIMULATION OF THE PROSTAGLANDIN-E2 OR THE BETA-ADRENERGIC RECEPTORS - RELATIONSHIP BETWEEN PKA ACTIVITY AND INHIBITION OF ANTI-CD3 MONOCLONAL ANTIBODY-INDUCED T-CELL PROLIFERATION [J].
BAUMAN, GP ;
BARTIK, MM ;
BROOKS, WH ;
ROSZMAN, TL .
CELLULAR IMMUNOLOGY, 1994, 158 (01) :182-194
[4]   Long-term dietary antioxidant supplementation reduces production of selected inflammatory mediators by murine macrophages [J].
Beharka, AA ;
Han, SN ;
Adolfsson, O ;
Wu, D ;
Smith, D ;
Lipman, R ;
Cao, G ;
Meydani, M ;
Meydani, SN .
NUTRITION RESEARCH, 2000, 20 (02) :281-296
[5]  
BEIQING L, 1997, CELL IMMUNOL, V182, P79
[6]   A signaling pathway to translational control [J].
Brown, EJ ;
Schreiber, SL .
CELL, 1996, 86 (04) :517-520
[7]   Proliferative responses of blood mononuclear cells (BMNC) in a cohort of elderly humans: role of lymphocyte phenotype and cytokine production [J].
Bruunsgaard, H ;
Pedersen, AN ;
Schroll, M ;
Skinhoj, P ;
Pedersen, BK .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2000, 119 (03) :433-440
[8]  
Cerdan C, 2000, BLOOD, V96, P420
[9]   Aging and T-cell-mediated immunity [J].
Chakravarti, B ;
Abraham, GN .
MECHANISMS OF AGEING AND DEVELOPMENT, 1999, 108 (03) :183-206
[10]   ANTIOXIDANTS INHIBIT PROLIFERATION AND CELL-SURFACE EXPRESSION OF RECEPTORS FOR INTERLEUKIN-2 AND TRANSFERRIN IN LYMPHOCYTES-T STIMULATED WITH PHORBOL-MYRISTATE ACETATE AND IONOMYCIN [J].
CHAUDHRI, G ;
HUNT, NH ;
CLARK, IA ;
CEREDIG, R .
CELLULAR IMMUNOLOGY, 1988, 115 (01) :204-213