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Signal Transduction Changes in T-cells with Aging

  • Tamas Fulop
  • Gilles Dupuis
  • Carl Fortin
  • Anis Larbi

Abstract

There are several functions of T-lymphocytes which are altered with aging. The cause is not exactly known. However the changes in T-lymphocyte activation could be caused by the altered T-cell receptor (TCR) signaling after ligation. The recently described membrane lipid rafts (MR) are critical to the assembly of the TCR, the CD28 coreceptor and the IL-2 receptor signaling machinery. The defect in IL-2 production by CD4+ T-cells with aging is not due to lower levels of expression of the TCR, CD28 or intracellular signaling molecules. However, there is a direct correlation between the activation of p56Lck and LAT at the cellular level and their association/recruitment with the lipid raft fractions of CD4+ and CD8+ T-cells. p56Lck , LAT and Akt/PKB are weakly phosphorylated in MR of stimulated CD4+ T-cells of elderly ascompared to young donors. Moreover, MR undergo changes in their lipid composition (ganglioside M1, cholesterol) with aging. There exists a differential role for lipid rafts in CD4+ and CD8+ T-cell activation with aging and consequently a differential localization of CD28 which may explain disparities in response to stimulation in human aging, mainly affecting the CD4+ T-lymphocyte population.

T-cells CD4+ T-cells CD8+ T-cells Lipid rafts Signal transduction Aging Cholesterol CD28 Coreceptor 

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© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Tamas Fulop
    • 1
  • Gilles Dupuis
    • 2
  • Carl Fortin
    • 3
  • Anis Larbi
    • 4
  1. 1.Research Center on Aging, Department of Medicine Immunology Graduate Programme, Faculty of MedicineUniversity of SherbrookeSherbrookeCanada
  2. 2.Clinical Research Center, Department of Biochemistry Immunology Graduate Programme, Faculty of MedicineUniversity of SherbrookeSherbrookeCanada
  3. 3.Clinical Research Center, Immunology Graduate Programme, Faculty of MedicineUniversity of SherbrookeSherbrookeCanada
  4. 4.Center for Medical Research Section for Transplant-Immunology and Immuno-Hematology Tuebingen Aging and Tumor Immunology groupUniversity of TuebingenTuebingenGermany

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