CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance. Academic Article uri icon

Overview

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.

authors

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

publication date

  • June 15, 2004

Research

keywords

  • Antigens, Differentiation
  • Immune Tolerance
  • Lymphocyte Activation
  • Th1 Cells

Identity

Scopus Document Identifier

  • 2942586924

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.172.12.7442

PubMed ID

  • 15187122

Additional Document Info

volume

  • 172

issue

  • 12