CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance

Todd N. Eagar, Danielle M. Turley, Josette Padilla, Nitin J. Karandikar, Litjen Tan, Jeffrey A. Bluestone, Stephen D. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7442-7450
Number of pages9
JournalJournal of Immunology
Volume172
Issue number12
DOIs
StatePublished - Jun 15 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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