Induction of antigen-specific human CD4(+) T cell anergy by peripheral blood DC2 precursors. Academic Article uri icon

Overview

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-alpha-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-gamma 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.

publication date

  • September 1, 2001

Research

keywords

  • Autoimmunity
  • Blood
  • CD4-Positive T-Lymphocytes
  • Clonal Anergy
  • Dendritic Cells
  • Self Tolerance

Identity

Scopus Document Identifier

  • 0034812464

Digital Object Identifier (DOI)

  • 10.1002/1521-4141(200109)31:9<2547::aid-immu2547>3.0.co;2-j

PubMed ID

  • 11536152

Additional Document Info

volume

  • 31

issue

  • 9