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Costimulation and autoimmunity
Authors:Elizabeth A TivolA Nicola Schweitzer  Arlene H Sharpe
Affiliation:The Blood Center of Southeastern Wisconsin, Milwaukee, WI 53201-2178, USA;Immunology Research Division, Department of Pathology, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115, USA
Abstract:The past year has seen significant advances in our understanding of the role of the B7-CD28/CTLA-4 pathway in T cell activation and self-tolerance. Recent studies have demonstrated that CTLA-4 is a critical negative regulator of T cell activation and autoreactivity, revealing a previously unsuspected means by which costimulation is involved in the maintenance and breakdown of self-tolerance. Manipulation of this costimulatory pathway in animal models of autoimmunity has shown an important role for this pathway in both the initiation and progression of autoimmune diseases.
Keywords:Abbreviations: APC antigen-presenting cell   CNS central nervous system   EAE experimental autoimmune encephalomyelitis   IL interleukin   mAb monoclonal antibody   MBP myelin basic protein   MS multiple sclerosis   NOD nonobese diabetic   PLP proteolipid protein   PTP protein tyrosine phosphatase   R receptor   R-EAE relapsing-remitting EAE   SEB staphylococcal enterotoxin B   TCR T cell receptor   TNF tumor necrosis factor
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