Induction of antigen-specific human CD4+ T cell anergy by peripheral blood DC2 precursors

Masataka Kuwana, Junichi Kaburaki, Timothy M. Wright, Yutaka Kawakami, Yasuo Ikeda

Research output: Contribution to journalArticle

128 Citations (Scopus)

Abstract

Dendritic cells (DC) are antigen (Ag)-presenting cells that are essential for initiation of T cell-dependent immunity, and distinct DC subsets are known to direct different classes of immune responses. DC2 precursors (pDC2) or plasmacytoid DC were recently identified as a Th2-skewing and IFN-α-producing human DC subset. Here, we demonstrate that pDC2 enriched from human peripheral blood have a capacity to induce an anergic state in human Ag-specific CD4+ T cell lines. Tetanus toxoid-specific T cell lines incubated with tetanus toxoid-pulsed autologous pDC2 failed to proliferate in secondary cultures with optimal Ag stimulation. T cell anergy induction required TCR engagement with Ag/MHC complex presented on pDC2. T cells rendered anergic lost IL-2 production but produced IFN-γ and IL-10 upon stimulation. The pDC2-induced unresponsiveness was completely or partially reversible when a high concentration of exogenous IL-2 was added in the secondary cultures. Autoreactive CD4+ T cell clones specific for topoisomerase I derived from a patient with scleroderma were also rendered anergic after co-culture with topoisomerase I-pulsed autologous pDC2, resulting in failure to proliferate or provide help to B cells. These results suggest that pDC2 are involved in maintenance of peripheral T cell tolerance and have potential for use in the suppression of pathogenic T cell responses in autoimmune diseases and organ transplantation.

Original languageEnglish
Pages (from-to)2547-2557
Number of pages11
JournalEuropean Journal of Immunology
Volume31
Issue number9
DOIs
Publication statusPublished - 2001 Oct 8

    Fingerprint

Keywords

  • Anergy
  • Antigen-presenting cell
  • Autoimmunity
  • Costimulation
  • Dendritic cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this