High-level expression of B7-H1 molecules by dendritic cells suppresses the function of activated T cells and desensitizes allergen-primed animals
Abstract
A body of evidence indicates that expression of the programmed cell death 1 (PD-1) receptor by activated T cells plays an important role in the down-regulation of immune responses; however, the functions of its known ligands, B7-H1 (PD-L1) and B7-dendritic cell (DC; PD-L2), at the effector phase of immune responses are less clear. In the current study, we investigated the roles of B7-H1 in DC-mediated regulation of hapten-activated T cells and the delayed-type contact hypersensitivity response in primed animals. We found that the expression of B7-H1 and B7-DC was induced on activation of DC by hapten stimulation. Blockade of B7-H1, but not B7-DC, enhanced the activity of hapten-specific T cells. Interaction with a DC line that expresses high cell-surface levels of B7-H1 (B7-H1/DC) suppressed the proliferation of, and cytokine production by, activated T cells. In vivo administration of hapten-carrying B7-H1/DC desensitized the response of sensitized animals to hapten challenge, and this desensitization was hapten-specific. These data indicate that B7-H1 expressed by DC mediates inhibitory signals for activated T cells and suppresses the elicitation of immune responses. The ability of B7-H1/DC to inhibit the function of preactivated T cells in vivo suggests novel strategies for the treatment of immune response-mediated disorders.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 03, 2006
- Source ID
- 10.1189/jlb.0805436
Entities
People
- Craig Elmets
- Feng Xu
- Guorui Zu
- Hee Kyung Kim
- Hongbing Guan
- Hui Li
- Hui Xu
- Lizhi Wu
- Yangxin Fu
Organizations
- National Center for Research Resources
- National Institutes of Health
- United States Department of Defense
- University of Alabama at Birmingham
- University of Chicago