Synergy between intraepithelial lymphocytes and lamina propria T cells drives inflammation during infection (161.12)

TL;DRAbstract

Abstract Oral infection of C57BL/6 mice with the protozoan parasite Toxoplasma gondii triggers severe necrotic lesions in the ileum within 7-10 days of cyst inoculation. Lesion development is mediated by Th-1 cytokines and CD4+ T cells. Pathology is associated with a shift in gut flora to predominantly gram-negative species and sub-epithelial bacterial translocation. As such, these features share striking similarity to inflammatory bowel diseases in humans, in particular Crohn’s disease. Recently, we uncovered an unexpected role for IFN-γ-dependent intraepithelial lymphocytes (IEL) in mediating ileal pathology after Toxoplasma infection. We show here that αβ and not γδ T cell receptor-positive IEL mediate intestinal damage. By adoptive transfer of mucosal T cells into naive Rag1-/- mice, we definitively establish that lesions are caused by pathogen-induced immunological factors rather than parasite-mediated tissue destruction. Furthermore, we demonstrate that IEL do not act alone to ca

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