The gut-associated immune system protects the host from a myriad of commensal bacteria while defending against orally invasive pathogens and mounting tolerance towards food antigens to control food allergies. Severe combined immunodeficient babies or immunosuppressed patients, either children or adults, who undergo bone marrow transplantation and suffer graft vs. host disease, have increased morbidity due to the lack of a functional gastrointestinal immune system. The overall hypothesis is that human cord blood stem cells can be used to investigate the development of a human immune system in the gut of immunodeficient mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) and mechanistically determine the conditions necessary to successfully generate (or recover) human SIgA in the gut lumen, which is the gold standard for an intact functional gastrointestinal immune system.
This project specifically aims to analyze in transplanted mice: 1) the presence of Peyer's patches and their T- and B-cell populations; 2) the presence of T cells and IgA plasma cells in the gut lamina propria, and of T and NKT cells in the intestinal intraepithelium; 3) the existence of SIgA in the gut lumen; and 4) the ability to respond to a pathogen challenge. This investigation will evaluate interventions that can most efficiently promote recovery of mucosal immunity, and therefore, protect the host from opportunistic infections of the gastrointestinal tract. Furthermore, the knowledge acquired will promote a better understanding of the mechanisms behind mucosal immune alterations that can lead to food allergies vs. malnutrition.
Lopez MC, Palmer BE, Lawrence DA. Phenotypic differences between cord blood and adult peripheral blood. Cytometry B Clin Cytom. 2008 Jul 18;76B(1):37-46.
Lopez MC, Lawrence DA. Proficiency testing experience for viable CD34+ stem cell analysis. Transfusion. 2008 Jun;48(6):1115-21.
Lopez MC, Holmes N. Phenotypical and functional alterations in the mucosal immune system of CD45 exon 9 KO mice. Int Immunol. 2005 Jan;17(1):15-25.