T-Bet Expression by Dendritic Cells Is Required for the Repolarization of Allergic Airway Inflammation
Document Type
Article
Publication Date
9-1-2008
Description
By cross-linking B7-DC on dendritic cells (DC) the human IgM antibody (B7-DC XAb) shifts polarized immune responses from Th2 to Th1 in an antigen-specific manner. The molecular determinants governing the ability of DC to reprogram the polarity of T cell recall responses are not yet known. In addition to the expected role of T-bet expressed by T cells in regulating Th1 responses, we find using in vitro assays and an established in vivo model of allergic airway inflammation that T-bet expression by DC is also required for the polarity shift promoted by B7-DC XAb. T-bet expression by both T cells and DC is critically important for B7-DC XAb-induced down-regulation of IL-4, up-regulation of IFN-γ and suppression of allergic airway inflammation. Moreover, retroviral reconstitution of T-bet expression in T-bet-deficient DC rescued their ability to modulate both naive and memory T-cell responses from Th2 to Th1. Our observations further our understanding of the critical mediators controlling the ability of DC to modify the responses of previously activated T cells and reveal the interesting use of the same transcription factor to regulate the inductive phenotype of DC and the inducible phenotype of T cells.
Citation Information
Heckman, Karin; Radhakrishnan, Suresh; Peikert, Tobias; Iijima, Koji; McGregor, Hugh C.; Bell, Michael P.; Kita, Hirohito; and Pease, Larry R.. 2008. T-Bet Expression by Dendritic Cells Is Required for the Repolarization of Allergic Airway Inflammation. European Journal of Immunology. Vol.38(9). 2464-2474. https://doi.org/10.1002/eji.200737952 PMID: 18819071 ISSN: 0014-2980