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

Citation
M. Kuwana et al., Induction of antigen-specific human CD4(+) T cell anergy by peripheral blood DC2 precursors, EUR J IMMUN, 31(9), 2001, pp. 2547-2557
Citations number
38
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
EUROPEAN JOURNAL OF IMMUNOLOGY
ISSN journal
0014-2980 → ACNP
Volume
31
Issue
9
Year of publication
2001
Pages
2547 - 2557
Database
ISI
SICI code
0014-2980(200109)31:9<2547:IOAHCT>2.0.ZU;2-N
Abstract
Dendritic cells (DC) are antigen (Ag)-presenting cells that are essential f or initiation of T cell-dependent immunity, and distinct DC subsets are kno wn to direct different classes of immune responses. DC2 precursors (pDC2) o r plasmacytoid DC were recently identified as a Th2-skewing and IFN-alpha - producing human DC subset. Here, we demonstrate that pDC2 enriched from hum an peripheral blood have a capacity to induce an anergic state in human Ag- specific CD4(+) T cell lines. Tetanus toxoid-specific T cell lines incubate d with tetanus toxoid-pulsed autologous pDC2 failed to proliferate in secon dary cultures with optimal Ag stimulation. T cell anergy induction required TCR engagement with Ag/MHC complex presented on pDC2. T cells rendered ane rgic 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 cult ures. Autoreactive CD4(+) T cell clones specific for topoisomerase I derive d from a patient with scleroderma were also rendered anergic after co-cultu re with topoisomerase I-pulsed autologous pDC2, resulting in failure to pro liferate or provide help to B cells. These results suggest that pDC2 are in volved in maintenance of peripheral T cell tolerance and have potential for use in the suppression of pathogenic T cell responses in autoimmune diseas es and organ transplantation.