Dendritic cells (DCs) serve as sentries for the immune system. DCs recognize foreign compounds (antigens) in the body, which they internalize and process. When DCs uptake foreign antigens, they migrate to secondary lymphoid organs, where the processed antigens are presented to T cells. Various DC subsets with unique cell lineages, surface protein markers, and tissue localization determinants have been identified. For example, Langerhans cells (LCs) and interstitial dendritic cells (intDCs) are DCs found in stratified epithelia, such as the skin. Though both are expressed in the skin, they differ with respect to their origin and surface protein content and can activate distinct types of immune responses. They may also have different specificities for the capture of antigens and presentation to circulating T cells. To date, it is unknown what role, if any, the different DC populations that reside or repopulate in the skin play in the development and progression of skin graft-versus-host disease (GVHD) following bone marrow transplant.
Study Type
OBSERVATIONAL
Enrollment
50
Washington University School of Medicine
St Louis, Missouri, United States
RECRUITINGDendritic cell characteristics
* Both GVHD affected and unaffected skin sections will be analyzed by immunostaining and the types of cells and strains of skin microbiota present will be analyzed * The different isolated DCs will be activated by different stimuli and will be characterized by gene (DNA, RNA sequencing or arrays) and multicolor flow cytometry analysis.
Time frame: Up to 2 years
Antigen specific lymphocyte subset characteristics
* Both GVHD affected and unaffected skin sections will be analyzed by immunostaining and the types of cells and strains of skin microbiota present will be analyzed * CD4+ and CD8+ T cells or other lymphocyte populations will be isolated from peripheral blood by fluorescence activated cell sorting. The DC subsets purified from the skin tissue will be used to stimulate these T cell populations. This will be followed by thorough characterization of the charged T cell populations by a variety of methods. These will include assays to measure proliferation, gene array analysis cytokine secretion and other functions of the charged T cells.
Time frame: Up to 2 years
Genes and skin microbiota that correlate with dendritic cell function
Time frame: Up to 2 years
Potential treatment targets as measured by deep sequencing or microarray analysis
Time frame: Up to 2 years
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