Modulation of human lymphocyte proliferative response with aging

Nadine Douziech, I. Seres, Anis Larbi, Edit Szikszay, Pierre Michel Roy, Marcel Arcand, Gilles Dupuis, Tamàs Fulop

Research output: Contribution to journalArticle

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Abstract

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-β-cyclodextrin, MBCD), or by using antioxidant vitamins (Vitamin E or C). 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.

Original languageEnglish
Pages (from-to)369-387
Number of pages19
JournalExperimental Gerontology
Volume37
Issue number2-3
DOIs
Publication statusPublished - Jan 3 2002

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Lymphocytes
Aging of materials
Vitamin E
Modulation
T-cells
Ascorbic Acid
Calcimycin
Cyclodextrins
T-Lymphocytes
Chemical activation
Cholesterol
Membranes
Cholera Toxin
Ionophores
Pertussis Toxin
p38 Mitogen-Activated Protein Kinases
Lymphocyte Activation
Mitogens
Isoproterenol
Vitamins

Keywords

  • Aging
  • Cyclodextrin
  • Membrane rafts
  • Mitogen-activated protein kinase
  • Proliferation
  • Signal transduction
  • T lymphocytes
  • TcR/CD3 complex
  • Vitamin C
  • Vitamin E

ASJC Scopus subject areas

  • Ageing
  • Medicine(all)

Cite this

Douziech, N., Seres, I., Larbi, A., Szikszay, E., Roy, P. M., Arcand, M., ... Fulop, T. (2002). Modulation of human lymphocyte proliferative response with aging. Experimental Gerontology, 37(2-3), 369-387. https://doi.org/10.1016/S0531-5565(01)00204-2

Modulation of human lymphocyte proliferative response with aging. / Douziech, Nadine; Seres, I.; Larbi, Anis; Szikszay, Edit; Roy, Pierre Michel; Arcand, Marcel; Dupuis, Gilles; Fulop, Tamàs.

In: Experimental Gerontology, Vol. 37, No. 2-3, 03.01.2002, p. 369-387.

Research output: Contribution to journalArticle

Douziech, N, Seres, I, Larbi, A, Szikszay, E, Roy, PM, Arcand, M, Dupuis, G & Fulop, T 2002, 'Modulation of human lymphocyte proliferative response with aging', Experimental Gerontology, vol. 37, no. 2-3, pp. 369-387. https://doi.org/10.1016/S0531-5565(01)00204-2
Douziech, Nadine ; Seres, I. ; Larbi, Anis ; Szikszay, Edit ; Roy, Pierre Michel ; Arcand, Marcel ; Dupuis, Gilles ; Fulop, Tamàs. / Modulation of human lymphocyte proliferative response with aging. In: Experimental Gerontology. 2002 ; Vol. 37, No. 2-3. pp. 369-387.
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