tailieunhanh - Báo cáo y học: "T-cell senescence and contraction of T-cell repertoire diversity – catalysts of autoimmunity and chronic inflammation"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: T-cell senescence and contraction of T-cell repertoire diversity – catalysts of autoimmunity and chronic inflammation. | Available online http content 5 5 225 Review Ageing autoimmunity and arthritis T-cell senescence and contraction of T-cell repertoire diversity -catalysts of autoimmunity and chronic inflammation Jorg J Goronzy1 2 and Cornelia M Weyand1 2 Department of Internal Medicine Mayo Clinic Rochester Minnesota USA 2Department of Immunology Mayo Clinic Rochester Minnesota USA Correspondence Jorg J Goronzy e-mail Received 8 May 2003 Revisions requested 25 Jun 2003 Revisions received 21 Jul 2003 Accepted 24 Jul 2003 Published 8 Aug 2003 Arthritis Res Ther 2003 5 225-234 DOI ar974 2003 BioMed Central Ltd Print ISSN 1478-6354 Online ISSN 1478-6362 Abstract Rheumatoid arthritis RA like many other autoimmune syndromes is a disease of adults with the highest incidence rates reported in the elderly. The immune system undergoes profound changes with advancing age that are beginning to be understood and that need to be incorporated into the pathogenetic models of RA. The age-related decline in thymic function causes extensive remodeling of the T-cell system. Age-dependent changes in T-cell homeostasis are accelerated in patients with RA. The repertoire of naive and memory T cells is less diverse possibly as a result of thymic insufficiency and it is biased towards autoreactive cells. Presenescent T cells emerge that are resistant to apoptosis and that often expand to large clonal populations. These cells are under the regulatory control of nonconventional costimulatory molecules display potent effector functions and appear to be critical in the synovial and extra-articular manifestations of RA. Keywords costimulation immunosenescence pathogenesis rheumatoid arthritis T-cell homeostasis Introduction During thymic development large arrays of clonally distributed a-p TCRs are generated that mediate the recognition of foreign peptides in the context of the appropriate MHC molecule. The theoretical diversity of the TCR repertoire is .