RETRACTED: B7-DC cross-linking restores antigen uptake and augments antigen-presenting cell function by matured dendritic cells

Abstract

Dendritic cells (DCs) are classified in two states: immature DCs (iDCs), which perform sentinel functions, sampling for antigen and danger signals, and mature DCs (mDCs), which exhibit enhanced antigen-presenting functions but are no longer capable of acquiring antigen. We now describe DCs with a different activation phenotype: cells having the strong antigen-presenting functions of mDCs and the antigen-acquiring functions of iDCs. We have described an antibody that binds the costimulatory molecule B7-DC and activates DCs. The resulting phenotype is distinct from iDCs or mDCs matured by using Toll-like receptor (TLR) agonists. Ability to take up antigen increases, while expression of B71/2 costimulatory and MHC molecules remains unchanged. DCs matured with TLR agonists and then superactivated through B7-DC exhibit a previously unrecognized phenotype. These DCs recover the ability to take up antigen, which is normally lost after treatment with TLR-3 and TLR-9 agonists, yet retain the high expression of costimulatory and MHC molecules and strong antigen-presenting functions of mDCs. Immunization using TLR agonists and B7-DC XAb (cross-linking antibody) together as adjuvant resulted in substantially increased cytolytic T cell responses, particularly when minimal peptide antigens were used. By stimulating DCs with two distinct activation signals, a previously unrecognized phenotype exhibiting augmented antigen-presenting functions was obtained

An Effective Vaccine Strategy Protective against Antigenically Distinct Tumor Variants

“…This antibody has been shown to interact with the B7 family member B7-DC and its activity includes restored antigen uptake in dendritic cells and the promotion of strong T cell responses (16,17). Furthermore, this antibody showed treatment potential against melanoma in both prophylactic and therapeutic regimens (18).…”

Induction of Autoimmunity by Expansion of Autoreactive CD4+CD62Llow Cells In Vivo

“…The precise function of B7-DC in vivo is presently unclear (36). Some reports indicate that B7-DC inhibits T cell responses via PD-1 while it enhances T cell activation by interacting with an as yet unidentified receptor (36,37). Our results show that increased expression of B7-DC on CD4 ϩ DC is related to the induction of CNS autoimmunity and further demonstrate differential in vivo regulation of B7-DC and its closest relative B7-H1.…”

The Multiple Personalities of the Chemokine Receptor CCR7 in Dendritic Cells

“…The stimulation of the endocytosis by CCR7 in the mature DCs is paradoxical because, as indicated above, DCs are known to reduce their endocytic ability when they differentiate into mature DCs, i.e., at the differentiation stage when they express CCR7 (1-3). However, it has also been shown that engagement of B7-DCs or CD40 in mature DCs also enhances the endocytosis in these cells (26). This finding suggest that B7-DCs, CD40 and CCR7, may belong to a group of surface molecules that can restore in the mature DCs the ability to uptake exogenous Ags, a feature typical of immature DCs.…”