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 acti- vation 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 expres- Signal Transduction Changes in T-cells with Aging Tamas Fulop, Gilles Dupuis, Carl Fortin and Anis Larbi Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 676 2 Signaling via TCR, CD28 and IL-2 Receptors and Their Changes with Aging . . . . . . . . 676 2.1 Receptors Involved in T-Lymphocyte Activation . . . . . . . . . . . . . . . . . . . . . . . . . . . 676 2.2 Membrane Lipid Raft Function and Composition . . . . . . . . . . . . . . . . . . . . . . . . . . 677 2.3 The Contribution of Membrane Lipid Rafts to the Altered-T-Lymphocyte Functions with Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 679 2.4 T-Cell Receptor Signalling and its Changes with Aging . . . . . . . . . . . . . . . . . . . . . 681 2.5 CD28 Dependent Signaling and Their Changes with Aging . . . . . . . . . . . . . . . . . . 683 2.6 Convergence of TCR/CD35.28 Signaling Pathways in T-cells Activation and Their Changes with Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 684 2.7 IL-2 Signalling and its Changes with Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 685 3 Membrane Lipid Rafts and Cytoskeleton . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 686 4 Negative Regulation of T-Lymphocyte Activation and its Changes with Aging . . . . . . . . 686 5 Membrane Composition Changes with Aging: Role of Cholesterol . . . . . . . . . . . . . . . . . 688 6 Do Membrane Rafts Properties Contribute to Human Immunosenescence? . . . . . . . . . . 689 7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 690 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 690 T. Fulop () Research Center on Aging, Department of Medicine Immunology Graduate Programme, Faculty of Medicine University of Sherbrooke, Sherbrooke, Quebec, Canada E-mail: tamas .fulop@usherbrooke.ca G. Dupuis Clinical Research Center, Department of Biochemistry Immunology Graduate Programme, Faculty of Medicine University of Sherbrooke, Sherbrooke, Quebec, Canada C. Fortin Clinical Research Center, Immunology Graduate Programme, Faculty of Medicine University of Sherbrooke, Sherbrooke, Quebec, Canada A. Larbi Center for Medical Research Section for Transplant-Immunology and Immuno-Hematology Tuebingen Aging and Tumor Immunology group University of Tuebingen, Germany T. Fulop et al. (eds.), Handbook on Immunosenescence, DOI 10.1007/ 978-1-4020-9062-2_35, © Springer Science+Business Media B.V. 2009 675