Year: 2002
Type: article
Abstract: T cell receptor engagement and the B7-CD28 / CTLA-4 signaling pathways play critical roles in T cell activation and regulation. CD28 engagement results in T cell activation, differentiation and survival while CTLA-4 signals block IL-2 production, cell cycle progression and T cell differentiation. We explored the role of CTLA-4 in peripheral tolerance induced by intravenous administration of ethylene carbodiimide-fixed, antigen-coupled splenocytes in the PLP139 - 151-induced relapsing experimental autoimmune encephalomyelitis system. Tolerance induction with PLP139 - 151-coupled splenocytes correlates with low B7 expression on the fixed antigen-presenting cells, conditions that would favor CTLA-4-mediated inhibition. Administration of CTLA-4Ig or anti-CTLA-4 concomitant with the 'tolerogenic' stimulus, however, failed to reverse tolerance induction. In contrast, blocking CTLA-4 at the time of secondary 'immunogenic' encounter with antigen reversed the tolerant state. These findings indicate that CTLA-4 is required to maintain the unresponsive state of the tolerized T cells upon antigenic stimulation under inflammatory conditions and, therefore, have important implications for therapeutic regulation of autoimmune disease.
Source: European Journal of Immunology
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
Awards: G1363034849, G1793072252, INDUCTION OF HOST-SPECIFIC TOLERANCE IN ALLOGENEIC BMT, G3100243555, G3284095179, COSTIMULATION IN PERIPHERAL T CELL TOLERANCE AND ANERGY, B7/CD28/CTLA-4 COSTIMULATION IN PATHOGENESIS OF R-EAE, G461244851, Pathogenesis and Immunoregulation of PLP-Induced R-EAE, G666159279, NOVEL CD28/CTLA4 COUNTER-RECEPTORS, Immunoregulation and Pathology of Chronic-Relapsing EAE
OpenAlex ID: W2066319119