International Immunology Advance Access originally published online on July 28, 2007
International Immunology 2007 19(8):993-1001; doi:10.1093/intimm/dxm077
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Concomitant increase of IL-10 and pro-inflammatory cytokines in intraepithelial lymphocyte subsets in celiac disease
1 Department of Clinical Microbiology, Immunology
2 Department of Clinical Sciences, Pediatrics, Umeå University, SE-90185 Umeå, Sweden
Correspondence to: M-L. Hammarström; E-mail: marie-louise.hammarstrom{at}climi.umu.se
Celiac disease (CD) is a small intestinal enteropathy caused by permanent intolerance to wheat gluten. Active disease is characterized by a prominent cytokine response of intraepithelial lymphocytes (IELs) to gluten-containing diet with concomitant increase in expression of pro-inflammatory IFN-
and down-regulatory IL-10 without increase in tumor necrosis factor-
(TNF-) or transforming growth factor-ß1 (TGF-ß1). The aim was to understand the local immune reaction by determining which intraepithelial T cell subsets produce the different cytokines. The three major IEL-subsets 
IELs, CD4+ßIELs and CD8+ßIELs, as well as CD94+CD8+ßIELs, selectively expanded in active CD, were retrieved from small intestinal biopsies of children with active CD and controls and analyzed quantitatively for cytokine mRNA expression. In active CD, CD8+ßIELs showed a significant increase in expression levels of both IFN- and IL-10. CD8+ßIELs were also the IEL subset with highest expression level per cell of both cytokines and constituted the cellular source for almost all IFN- and most IL-10. Expression levels of both cytokines were higher in CD94–CD8+ßIELs than CD94+CD8+ßIELs. TNF- levels were only increased in CD4+ßIELs, which also showed the highest expression level per cell and constituted the major source of this cytokine. Interestingly, IL-10 was increased also in CD4+ßIELs. Cytokine levels were low in IELs. ‘Classical’ CD94–CD8+ß T cells within the epithelium are responsible for the excessive production of IFN-, believed to drive the formation of intestinal lesions in active CD. Production of IL-10 may be a common feature of IELs producing pro-inflammatory cytokines, thereby attempting to limit inflammation in an autocrine fashion.
Keywords: IFN-, TNF-, TGF-ß, CD8+ T cell, CD94+ T cell
Transmitting editor: L. Moretta
Received 21 January 2007, accepted 29 May 2007.
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