Rheumatoid Arthritis: Larbi A

Larbi A, Fülöp T, Pawelec G. · Center for Medical Research (ZMF), Tübingen Aging and Tumour Immunology Group, Section for Transplantation Immunology and Immunohematology, University of Tübingen, Waldhörnlestrasse 22, D-72072 Tübingen, Germany. · Adv Exp Med Biol. · Pubmed #19065799 No free full text.

Abstract: Aging is associated with a myriad of changes including alterations in glucose metabolism, brain function, hormonal regulation, muscle homeostasis and the immune system. Aged dividuals, generally still defined as over 65 years old, differ from middle-aged or young donors in many features of the immune system. The major observation is that the elderly population is not able to cope with infections as well as younger adults and recovery generally takes longer. Moreover, some diseases first appear with advancing age and are likely associated with dysfunction of the immune system. Thus, Alzheimer's disease, atherosclerosis, type II diabetes and some autoimmune disorders are linked to changes in immune function. One major immune cell population implicated as being responsible for the initiation and chronicity of immune dysfunction leading to diseases or immunosuppression is the T-cell. Although many changes in B-cell and innate immune function in aging are associated with the appearance of disease, they are not as well studied and clearly demarcated as changes in the T-cell compartment. The adaptive immune system is coordinated by T-cells, the activation of which is required for the initiation, maintenance and termination of responses against pathogens. Changes in the expression and functions of the T-cell receptor (TCR) for antigen and its co-receptors are closely associated with immunosenescence. Certain similar changes have also been found in some other disease states, e.g., rheumatoid arthritis, systemic lupus erythematosus and cancer. In this chapter, we will summarize our knowledge about multichain immune recognition receptor signaling, mainly the TCR, in aging and autoimmune diseases.

Fülöp T, Larbi A, Dupuis G, Pawelec G. · Research Center on Ageing, Sherbrooke Geriatric University Institute, University of Sherbrooke, Quebec, Canada. · Arthritis Res Ther. · Pubmed #14680505 links to  free full text

Abstract: It is widely accepted that cell-mediated immune functions decline with age, rendering an individual more susceptible to infection and possibly cancer, as well as to age-associated autoimmune diseases. The exact causes of T-cell functional decline are not known. One possible cause could be the development of defects in the transduction of mitogenic signals following TCR stimulation. This T-cell hyporesponsiveness due to defects of signalling through the TCR either from healthy elderly subjects or from individuals with autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus results in an impaired ability to mount efficient immune responses and to maintain responsiveness to foreign antigens. This implies that a high proportion of autoreactive T cells might accumulate either intrathymically or in the periphery. T-cell anergy and differential TCR signalling could thus also be key players in the disruption of tolerance and the onset of autoimmune diseases. The increasing number of the elderly may lead to an increase of clinically important autoimmune diseases. We will review the signal transduction changes through the TCR-CD3 complex in T lymphocytes from healthy elderly subjects, which result in a modification of the activation of transcription factors involved in IL-2 gene expression leading to decreased IL-2 production. The putative contribution of altered T-cell signalling with ageing in the development of autoimmune diseases will be also discussed.