H. polygyrus infection mediates regulatory T cell function in the gut of mice.
Stoyanoff, Korynn.
2012
-
Abstract: Regulatory T cells are crucial for maintaining homeostasis in the body. These cells come in many varieties and serve different roles based on their location, induction, and protein repertoire. The transcription factor Foxp3, marks an especially important group of regulatory T cells that can further be divided based on their classification as CD4+ or CD8+ and their ability to produce othe... read morer factors such as the anti-inflammatory cytokine IL-10. Regulatory T cells are especially needed in the gut where the resident immune cells are continually exposed to a variety of antigens from both pathogenic and non-pathogenic sources. A lack of regulation leads to uncontrolled inflammation and colitis. The regulatory immune environment of the gut is enhanced following infection with the intestinal parasite Heligmosomoides polygyrus (H. poly). In this thesis project I have investigated four groups of regulatory T cells that reside in the gut and are enhanced following infection with H. poly. Following infection and when exposed to the helminth-induced cytokines TGF- and IL-2, Foxp3+CD8+ T cells are maintained in culture and Foxp3 expression is increased by two-fold. These findings coupled with functional assays suggest that these unique regulatory T cells are regulators of inflammation in the gut following infection with H. poly. Likewise, when Foxp3+ T cells are divided into Foxp3+IL-10+ and Foxp3+IL-10- T cells, TGF- and IL-2 also have an effect on regulatory cell maintenance. Foxp3+IL-10+ T cells, which are essential for preventing colitis, are preferentially maintained. In functional assays, H. poly infection altered the ability of Foxp3+IL-10+ T cells to inhibit proliferation. Molecular analysis of these Foxp3 subsets continues to reveal differences that may reveal their specific roles during H. poly infection. Finally, despite the strict requirement for gut homeostasis, I have shown that IL-10 can be inhibited by T cells in the gut in a helminth-dependent manner. All of these findings together show a very complex system of regulation that is reliant on T cells and further modified by infection with H. poly. This system of regulators illustrates how the gut immune system can prevent inflammation even in the constant presence of antigen. Having a better understanding of how these regulatory pathways work and are enhanced following H. poly infection is vital in the development of treatments for IBD in humans.
Thesis (Ph.D.)--Tufts University, 2012.
Submitted to the Dept. of Immunology.
Advisors: Joel Weinstock, and Thereza Imanishi-Kari.
Committee: Alexander Poltorak, and Linden Hu.
Keyword: Immunology.read less - ID:
- 5d86pb74z
- To Cite:
- DCA Citation Guide EndNote
