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2015 ; 148
(7
): 1417-26
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?? Intraepithelial Lymphocyte Migration Limits Transepithelial Pathogen Invasion
and Systemic Disease in Mice
#MMPMID25747597
Edelblum KL
; Singh G
; Odenwald MA
; Lingaraju A
; El Bissati K
; McLeod R
; Sperling AI
; Turner JR
Gastroenterology
2015[Jun]; 148
(7
): 1417-26
PMID25747597
show ga
BACKGROUND & AIMS: Intraepithelial lymphocytes that express the ?? T-cell
receptor (?? IELs) limit pathogen translocation across the intestinal epithelium
by unknown mechanisms. We investigated whether ?? IEL migration and interaction
with epithelial cells promote mucosal barrier maintenance during enteric
infection. METHODS: Salmonella typhimurium or Toxoplasma gondii were administered
to knockout (KO) mice lacking either the T cell receptor ? chain (Tcrd) or CD103,
or control TcrdEGFP C57BL/6 reporter mice. Intravital microscopy was used to
visualize migration of green fluorescent protein (GFP)-tagged ?? T cells within
the small intestinal mucosa of mice infected with DsRed-labeled S typhimurium.
Mixed bone marrow chimeras were generated to assess the effects of ?? IEL
migration on early pathogen invasion and chronic systemic infection. RESULTS:
Morphometric analyses of intravital video microscopy data showed that ?? IELs
rapidly localized to and remained near epithelial cells in direct contact with
bacteria. Within 1 hour, greater numbers of T gondii or S typhimurium were
present within mucosae of mice with migration-defective occludin KO ?? T cells,
compared with controls. Pathogen invasion in Tcrd KO mice was quantitatively
similar to that in mice with occludin-deficient ?? T cells, whereas invasion in
CD103 KO mice, which have increased migration of ?? T cells into the lateral
intercellular space, was reduced by 63%. Consistent with a role of ?? T-cell
migration in early host defense, systemic salmonellosis developed more rapidly
and with greater severity in mice with occludin-deficient ?? IELs, relative to
those with wild-type or CD103 KO ?? IELs. CONCLUSIONS: In mice, intraepithelial
migration to epithelial cells in contact with pathogens is essential to ?? IEL
surveillance and immediate host defense. ?? IEL occludin is required for early
surveillance that limits systemic disease.