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Baylor Institute for Immunology Research
3434 Live Oak St.
Dallas, Texas 75204
PWSBIIR@baylorhealth.edu
Tel: (214) 820-7451
Fax: (214) 820-4813
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Technical Development: Human Dendritic Cell Subsets
PI: Jacques Banchereau, Ph.D.
Vaccines and antibiotics help prevent or ameliorate many infectious diseases. Yet, natural evolution and engineering for bioterrorism purposes create novel biothreats for which novel vaccines may represent the most potent countermeasures. We now know that vaccines act through dendritic cells (DCs), the initiators and controllers of immune effectors (T and B lymphocytes) differentiation. Just as lymphocytes are composed of different subsets, DCs comprise several subsets that differentially control lymphocyte function. Unfortunately, there is a shortage of reagents that permit to distinguish these subsets at various stages of differentiation. While it is now recognized that pathogens target DCs, it is not known which subsets are affected and how. Here, we will develop, validate and standardize assays, reagents and technologies for studies in human DC subsets in vitro and in vivo.
Aim 1 will generate mAbs specific for human DC subsets at distinct stages of maturation and establish mRNA microarray biosignatures of DC subsets exposed in vitro to Category B-C pathogens.
Aim 2 will generate mice with a full human immune system for testing vaccine potency, microbe pathogenicity and establish in vivo biosignatures of Category B-C pathogens.
Aim 3 will establish assays for in vitro and in vivo analysis of how Category B-C pathogens alter biology of human DC subsets.
Aim 4 will establish methodologies for in vivo analysis of how Category B-C pathogens alter interactions of human DC subset with immune effectors.
This Technical Development project will enhance our knowledge of human DC subsets and create tools for evaluation of human vaccines.
Subcontract Tech Dev
PI: Ira Mellman, PhD
Yale University
This project will be to develop, validate and standardize assays, reagents and technologies for studies in Human Immunology
• To provide human Dendritic Cells (DCs) subsets to all investigators of the Center, establish their mRNA expression patterns, establish NIAID Category B-C pathogen biosignatures, and generate monoclonal antibodies distinguishing the different DC subsets at different stages of maturation.
• To generate mice with human immune system: Humouse. It will provide humanized NOD-SCID mice to virtually all the investigators of the Center. It will establish the biosignatures of NIAID Category B-C pathogens.
• To establish assays for the analysis of cell biology of the different human DC subsets in vitro and in vivo and determine how NIAID Category B-C pathogens alter their Antigen-presenting capacity.
• To establish methodologies for analysis of how the different human DC subsets interact with immune effectors in vivo and will determine how NIAID Category B-C pathogens alter DC migration in vivo and their interactions with immune effectors.
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