Publication Date

Fall 2015

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

Advisor

Tzvia Abramson

Keywords

Celiac Disease, Crohn's Disease, IBD, iNKT Cells, Pediatric, Ulcerative Colitis

Subject Areas

Immunology; Microbiology; Molecular biology

Abstract

The incidence of chronic intestinal diseases such as Crohn’s disease (CD), ulcerative colitis (UC), and celiac disease is steadily rising in pediatric patients in the United States. Although there is an influx of helper T cells to the gastrointestinal (GI) tract in these diseases, the immunopathologic mechanisms of specific T cell subsets are not clearly understood and diagnosis between these diseases is difficult. We hypothesized that the frequency of specific subsets of circulating invariant natural killer T (iNKT) cells and their surface trafficking receptor (TR) phenotype indicate location and degree of inflammation in patients and further help to distinguish between these chronic intestinal diseases. We performed a multi-color flow cytometry analysis on peripheral blood (PB) CD8- and CD8+ iNKT cells in pediatric patients in the non-active and active disease states with CD (n=6), UC (n=7), celiac disease (n=2) and healthy donors (HDs) (n=7). The average frequency of circulating CD8- and CD8+ iNKT cells in patients with non-active and active disease states was significantly increased in comparison to HD. A greater percentage of the CD8- iNKT cells in UC patients expressed the gut-homing TRs α4β7 and GRPR15 indicative of cell migration to the large intestine. In sum, circulating iNKT cells were elevated in patients with these chronic intestinal diseases. Screening specific subsets of iNKTs may provide a more efficient form of distinguishing between UC, CD and Celiac disease and may potentially be used as a complementary approach to monitoring disease activity or therapeutic efficacy in pediatric patients.

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