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The research conducted in our laboratory focuses on basic biological questions related to mucosal immunology. The generation of immune responses requires intimate cell-to-cell contact between antigen presenting cells (APC) and T-cells. Given the specificity and almost limitless diversity of the T-cell receptor repertoire, only a few of the estimated 25 million naïve T-cell clones in a human has the capacity to recognize a specific antigen. The immune system has evolved specialized microenvironments, or organized lymphoid structures, to facilitate this cell-cell interaction and overcome the improbability of this event. Within the intestine, a new class of organized lymphoid structures-isolated lymphoid follicles (ILFs)-has recently been identified. Similar to classical secondary lymphoid structures, ILFs act as inductive sites for immune response. However in contrast to these structures, which are static in number and location, ILFs can form or regress throughout life in response to local environmental cues. We are actively investigating the cellular and molecular pathways involved in lymphoid structure development using ILFs as a model system. These findings will translate to broader areas of health and disease, including mucosal vaccination, and conditions associated with the formation of ectopic lymphoid structures, such as autoimmune and chronic inflammatory diseases.
gastro.wustl.edu/faculty/newberry.html
The Technique
Studies of lymphoid structure development have been technically challenging. Classic or secondary lymphoid structure formation occurs at specific times during gestation, necessitating that studies be carried out on carefully timed embryonic tissue. Furthermore, the number of lymphoid structures that can be examined in one embryo is relatively limited. The identification of a new class of organized lymphoid structures, ILFs, has alleviated some of these limitations. ILF development recapitulates events of secondary lymphoid structure development, with a salient difference being that ILFs continuously form and regress throughout life. The normal intestine of an adult contains approximately 1000 of these structures in various stages of maturity. Using the technique we describe in our paper, we can rapidly enumerate all the structures within the intestine in the entire spectrum of ILF development. Thus, studies of a few animals can provide information on the growth of thousands of structures. Our technique, combined with induced mutant mouse strains, bone marrow chimeric mice, and blockade of specific pathways is a powerful tool that allows us to rapidly identify the pathways important for the progression of organized lymphoid structures, and to place these pathways and factors in a chronological and cellular context.
Whole-mount techniques to evaluate subepithelial cellular populations in the adult mouse intestine, p. 50.
