Peptide-activated double-negative T cells can prevent autoimmune type-1 diabetes development

Megan S. Ford, Wenhao Chen, Sophie Wong, Carmen Li, Ramesh Vanama, Alisha R. Elford, Sylvia L. Asa, Pamela S. Ohashi, Li Zhang

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Autoimmune diseases may develop because of defective maturation, activation, differentiation and function of regulatory T cells. Previous studies have shown that exposure to donor antigen activates peripheral TCRαβ+CD3+CD4- CD8-NK1.1-, double-negative (DN) T cells, which specifically suppress anti-donor T cells and enhance survival of skin and heart grafts from allogeneic and xenogeneic donors. However, the role of DN T cells in preventing T cell-mediated autoimmune disease is unknown. Here, we analyzed the ability of DN T cells to recognize peptides expressed on self MHC and to suppress peptide-reactive CD8+ T cells, using the P14 mouse model that expresses a transgenic TCR specific for gp33 peptide presented on self MHC class I-Db. We found that injection of gp33 peptide resulted in increased DN and decreased CD8+ T cell numbers in the lymph nodes when compared to untreated mice. Injection of gp33, but not TCR-non-specific AV peptide, increased expression of T cell activation markers on DN T cells. Moreover, gp33-activated DN T cells suppressed proliferation of syngeneic CD8+ T cells via killing activated CD8+ T cells in an antigen-specific fashion in vitro. Furthermore, transferring gp33-activated DN T cells inhibited the development of autoimmune diabetes, suggesting that DN T cells may provide a novel therapy for T cell-mediated autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)2234-2241
Number of pages8
JournalEuropean Journal of Immunology
Volume37
Issue number8
DOIs
StatePublished - Aug 2007

Keywords

  • Autoimunity
  • Immune regulation
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Peptide-activated double-negative T cells can prevent autoimmune type-1 diabetes development'. Together they form a unique fingerprint.

Cite this