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Intestinal Antigen Presenting Cells and Immune Regulation

Investigators
Brown, Kurt
Institutions
Children's Hospital - Philadelphia
Start date
1996
End date
2002
Objective
To further investigate the immunologic basis for these differences we will answer the following questions: 1) Which APCs (macrophages, B cells, follicular dendritic cells, villous epithelial cells) contain rotavirus antigens after oral inoculation of mice with a strain relatively well-adapted to growth at the intestinal mucosal surface? 2) What are the relative capacities of purified populations of APCs to present rotavirus antigens after oral inoculation with infectious rotavirus? 3) To what extent are the types or frequencies of APCs involved after oral inoculation with infectious rotavirus altered by inoculation with microencapsulated virus, virus strains less adapted to replication at the intestinal surface (including inactivated virus) or viral proteins? 4) To what extent are the viral proteins recognized by virus-specific neutralizing antibodies and virus-specific CTLs altered by selection of specific APC types?
More information
Antigen presenting cells (APCs) initiate and modulate virus-specific humoral and cellular immune responses. Much has been learned about relative differences in the capacities of APCs such as B cells, macrophages, follicular dendritic cells, and mucosal epithelial cells to process and present viral proteins and drive virus-specific B cell or cytotoxic T lymphocyte (CTL) responses. However, little is known about the capacity of different APC types to alter the balance between or structural specificities of virus-specific humoral and cellular immune responses. An understanding of these interactions will be critical in developing successful vaccine strategies. Using the intestinal pathogen, rotavirus, our laboratory has characterized virus-specific humoral and cellular immune responses in the gut-associated lymphoid tissue (GALT) of mice after oral inoculation. We have determined the viral proteins recognized by virus-specific neutralizing antibodies and virus-specific CTLs after oral inoculation of mice with a rotavirus strain well-adapted to growth in intestinal epithelial cells. In addition, we have demonstrated distinct differences in the balance between humoral and cellular immune responses depending on the relative capacity of virus strains to replicate at the intestinal mucosal surface. We have also demonstrated an enhanced virus-specific humoral response after microencapsulation of rotavirus in a novel aqueous-based system developed in our lab.
Funding Source
Nat'l. Inst. of Diabetes and Digestive and Kidney Diseases
Project number
5K08DK002382-05
Categories
Bacterial Pathogens
Viruses and Prions
Escherichia coli