CTLA-4 Regulates Expansion and Differentiation of Th1 Cells Following Induction of Peripheral T Cell Tolerance
Year: 2004
Type: article
Abstract: Intravenous treatment with Ag (peptide)-coupled, ethylene carbodiimide-fixed syngeneic splenocytes (Ag-SP) is a powerful method to induce anergy in vitro and peripheral T cell tolerance in vivo. In this study, we examined the effects of Ag-SP administration on T cell activity ex vivo and in vivo using OVA-specific DO11.10 TCR transgenic T cells. Although treatment with OVA323-339-SP resulted in a strong inhibition of peptide-specific T cell recall responses in vitro, examination of the immediate effects of Ag-SP treatment on T cells in vivo demonstrated that tolerogen injection resulted in rapid T cell activation and proliferation. Although there was an increase in the number of OVA-specific DO11.10 T cells detected in the lymphoid organs, these previously tolerized T cells were strongly inhibited in mounting proliferative or inflammatory responses upon rechallenge in vivo with peptide in CFA. This unresponsiveness was reversible by treatment with anti-CTLA-4 mAb. These results are consistent with the hypothesis that Ag-SP injection induces a state of T cell anergy that is maintained by CTLA-4 engagement.
Source: The 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: W2105657402