The Role of B7 Ligand Interactions During an In Vivo Mucosal Immune Response
Abstract
The nematode parasite, B: polygyrus, has been extensively used as a model to study the type 2 in vivo immune response. This response is characterized by the development of ILA producing T cells which mediate the development of other allergy associated effector cell populations. Following oral inoculation with H. polygyrus larvae, the host rapidly develops a type 2 immune response characterized by intestal mastocytosis, blood eosinophilia, elevations in T cell IL-2R expression, in situ CD4+ T cell expansion and ILA production, and increases in B cell MHC class II expression, MLN 6C formation and serum IgE and IgGi levels. The costimulatory signal provided to naive T helper (Th) cells through CD28/CTLAA interactions is required for in vivo Th cell effector function associated with cytokine production. In this project, I examined whether the two well-characterized ligands for these molecules, B7-1 and B7-2, differentially influence the development of a type 1 or type 2 immune response. Administration of the combination of anti-B7-1 and anti-B7-2 mAbs inhibited H polygyrus-induced increases in serum IgG1 and IgE levels, the expansion of mesenteric lymph node (MLN) germinal centers, in situ CD4+ T cell expansion, elevated blood eosinophils, and increased intestinal mucosal mast cells. Similarly, both Abs blocked MLN and Peyer's Patch's patch cytokine gene expression and elevations in MLN T cell derived IL-4 protein secretion However, in the same experiments, administration of either anti-B7-1 and anti-B7-2 mAbs alone had little effect on these parameters. T cell and B cell activation was also blocked by the combination of anti-B7.2 and a B7-1 specific mutant Y100F CTLAIg construct. These results suggest that, to the extent that anti-B7-1 and anti-B7-2 mAbs block B7 interactions, either B7-1 or B7-2 ligand interactions can provide the required costimulatory signals that lead to T cell effector function during the type 2 in vivo immune response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1998
- Accession Number
- ADA442209
Entities
People
- Rebecca Greenwald
Organizations
- Uniformed Services University of the Health Sciences