title: Synergy between intraepithelial lymphocytes and lamina propria T cells drives intestinal inflammation during infection.
abstract: Oral infection of C57BL/6 mice with Toxoplasma gondii triggers severe necrosis in the ileum within 7-10 days of infection. Lesion development is mediated by Th-1 cytokines, CD4+ T cells, and subepithelial bacterial translocation. As such, these features share similarity to Crohn's disease. Recently, we uncovered a role for intraepithelial lymphocytes (IELs) in mediating pathology after Toxoplasma infection. We show here that αβ and not γδ T-cell IELs mediate intestinal damage. By adoptive transfer of mucosal T cells into naive Rag1⁻/⁻ mice, we demonstrate that IELs do not function alone to cause inflammatory lesions, but act with CD4+ T lymphocytes from the lamina propria (LP). Furthermore, recipient mice pretreated with broad-spectrum antibiotics to eliminate intestinal flora resisted intestinal disease after transfer of IELs and LP lymphocytes. Our data provide valuable new insights into the mechanisms of intestinal inflammation, findings that have important implications for understanding human inflammatory bowel disease.
authors.affiliation: Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA. cee22@cornell.edu
authors.forename: C E
authors.initials: CE
authors.lastname: Egan
authors.forename: K J
authors.initials: KJ
authors.lastname: Maurer
authors.forename: S B
authors.initials: SB
authors.lastname: Cohen
authors.forename: M
authors.initials: M
authors.lastname: Mack
authors.forename: K W
authors.initials: KW
authors.lastname: Simpson
authors.forename: E Y
authors.initials: EY
authors.lastname: Denkers
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D019072:Antibiotic Prophylaxis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication; D003424:Crohn Disease / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D007249:Inflammation; D007413:Intestinal Mucosa / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity; D014123:Toxoplasmosis / Q000276:immunology* / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta