A Novel Role for γδ Intraepithelial Lymphocyyrd in Antibacterial Defense of the Intestine

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Title: A Novel Role for γδ Intraepithelial Lymphocyyrd in Antibacterial Defense of the Intestine
Author: Ismail, Anisa Salim
Abstract: The mammalian intestine has coevolved with a highly complex population of enteric bacteria . For the most part , mammals and their intestinal microbiota maintain a mutually beneficial relationship . However , the symbiotic nature of this relationship depends on strict sequestration of intestinal microbes in the gut lumen , and damage to intestinal surfaces by chemical agents or microbial pathogens poses a serious threat of inflammation and sepsis . Therefore , the cells populating the intestinal epithelium have evolved strategies to maintain the integrity of the intestinal epithelium and to limit bacterial invasion . Gamma delta intraepithelial lymphocytes (gamma delta IEL ) are unconventional T cells that intercalate under epithelial tight junctions of the intestine . While gamma delta IEL are numerically the most abundant T cell population in the body , their biology in intestinal tissues has remained obscure . The work in this thesis seeks to understand the role of gamma delta IEL in maintaining homeostasis with symbiotic intestinal microbes and in protecting against bacterial pathogens . My findings disclose that intestinal bacteria provide critical regulatory input to gamma delta IEL in the small and large intestine , and direct the production of proinflammatory and antibacterial factors in gamma delta IEL . Additionally , my in vivo studies disclose a novel role for delta gamma IEL in antibacterial defense of the intestine , revealing that gamma delta IEL protect the mucosal barrier in two general ways . First , gamma delta IEL protect against opportunistically invading commensals immediately after mucosal damage . Next , they also function to limit dissemination of invasive bacterial pathogens . My work suggests that a unique feature of gamma delta IEL relative to other intestinal immune cells is their early role in providing protection against invading bacteria immediately after challenge . Taken together , these findings disclose that gamma delta IEL participate in multifaceted antibacterial responses to promote beneficial host -microbial relationships in the intestine .
URI: http : / /hdl .handle .net /2152 .5 /515
Date: 2009-09-04


A Novel Role for γδ Intraepithelial Lymphocyyrd in Antibacterial Defense of the Intestine. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /515 .

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