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

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.