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T-bet expression by dendritic cells is required for the repolarization of allergic airway inflammation.


ABSTRACT: 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-gamma 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.

SUBMITTER: Heckman KL 

PROVIDER: S-EPMC3730252 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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T-bet expression by dendritic cells is required for the repolarization of allergic airway inflammation.

Heckman Karin L KL   Radhakrishnan Suresh S   Peikert Tobias T   Iijima Koji K   McGregor Hugh C HC   Bell Michael P MP   Kita Hirohito H   Pease Larry R LR  

European journal of immunology 20080901 9


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 b  ...[more]

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