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Trends Mol Med. 2003 Nov;9(11):483-9.

Co-stimulation agonists as a new immunotherapy for autoimmune diseases.

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Department of Pathology and Committee in Immunology, University of Chicago, Chicago, IL 60637, USA.


Lymphocytes are important in the pathogenesis of many autoimmune diseases. Blocking co-stimulatory signals for T-cell activation has been widely used as an approach to treating autoimmunity, but it has encountered limited clinical success. Some agonistic monoclonal antibodies to co-stimulatory molecules greatly enhance immune responses mediated by T cells, such as antiviral, anti-tumor and alloresponses. Surprisingly, recent studies have demonstrated that these agonists have profound therapeutic effects on autoimmune diseases by potentially depleting autoreactive lymphocytes or by inhibiting their function. These findings imply that signaling through co-stimulatory molecules can have diametric outcomes in modulating immune responses, thereby providing a novel approach to the treatment of autoimmune diseases.

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