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Production of interferon‐γ by activated T‐cell receptor‐αβ CD8αβ intestinal intraepithelial lymphocytes is required and sufficient for disruption of the intestinal barrier integrity
Author(s) -
Zufferey Christel,
Erhart Dominik,
Saurer Leslie,
Mueller Christoph
Publication year - 2009
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2009.03110.x
Subject(s) - intraepithelial lymphocyte , t cell receptor , biology , barrier function , immunology , t cell , intestinal mucosa , cd8 , intestinal epithelium , microbiology and biotechnology , antigen , epithelium , immune system , medicine , genetics
Summary Maintenance of intestinal epithelial barrier function is of vital importance in preventing uncontrolled influx of antigens and the potentially ensuing inflammatory disorders. Intestinal intraepithelial lymphocytes (IEL) are in intimate contact with epithelial cells and may critically regulate the epithelial barrier integrity. While a preserving impact has been ascribed to the T‐cell receptor (TCR)‐γδ subset of IEL, IEL have also been shown to attenuate the barrier function. The present study sought to clarify the effects of IEL by specifically investigating the influence of the TCR‐αβ CD8αβ and TCR‐αβ CD8αα subsets of IEL on the intestinal epithelial barrier integrity. To this end, an in vitro coculture system of the murine intestinal crypt‐derived cell‐line mIC cl2 and syngeneic ex vivo isolated IEL was employed. Epithelial integrity was assessed by analysis of transepithelial resistance (TER) and paracellular flux of fluorescein isothiocyanate‐conjugated (FITC‐) dextran. The TCR‐αβ CD8αα IEL and resting TCR‐αβ CD8αβ IEL did not affect TER of mIC cl2 or flux of FITC‐dextran. In contrast, activated TCR‐αβ CD8αβ IEL clearly disrupted the integrity of the mIC cl2 monolayer. No disrupting effect was seen with activated TCR‐αβ CD8αβ IEL from interferon‐γ knockout mice. These findings demonstrate that secretion of interferon‐γ by activated TCR‐αβ CD8αβ IEL is strictly required and also sufficient for disrupting the intestinal epithelial barrier function.