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Signal Transduction Changes in T-cells with Aging

  • Chapter
Handbook on Immunosenescence

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.

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Authors and Affiliations

  1. Research Center on Aging, Department of Medicine Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Tamas Fulop

  2. Clinical Research Center, Department of Biochemistry Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Gilles Dupuis

  3. Clinical Research Center, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, Sherbrooke, Quebec, Canada

    Carl Fortin

  4. Center for Medical Research Section for Transplant-Immunology and Immuno-Hematology Tuebingen Aging and Tumor Immunology group, University of Tuebingen, Tuebingen, Germany

    Anis Larbi

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  2. Gilles Dupuis
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Editors and Affiliations

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, 1036 Rue Belvedere, J1H 4C4, Sherbrooke, Quebec, Canada

    Tamas Fulop

  2. Department of Experimental Pathalogy, CIG Interdepartmental Center “L. Galvani” University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, 4-6-22 Kohinato, Bunkyo-ku, Tokyo, 112-0006, Japan

    Katsuiku Hirokawa

  4. ZMF - Zentrum Med. Forschung Abt. Transplant./ Immunologie, University of Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany

    Graham Pawelec

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Fulop, T., Dupuis, G., Fortin, C., Larbi, A. (2009). Signal Transduction Changes in T-cells with Aging. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook on Immunosenescence. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9063-9_35

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