Intraepithelial lymphocytes in refractory celiac disease : lost in transition

Refractory coeliac disease type II (RCDII) is a severe complication of coeliac disease. Whereas celiac disease can successfully be treated by the strict avoidance of gluten, refractory celiac patients show no remission despite a gluten-free diet. The pathology of RCDII is only partially understood, but a key feature of RCDII is the expansion of aberrant CD3- intraepithelial lymphocytes (IEL) in the small intestinal epithelium. Whereas the majority of IEL generally are composed of CD3+ T cells, in RCDII CD3- IEL form 20-80% of the IEL population. In approximately 40% of RCDII patients these lymphocytes develop into a lethal, invasive lymphoma. In this thesis, we identify a potential physiological precursor to the (pre)malignant CD3- IEL found in RCDII patients, and compared the composition, phenotype and differentiation potential of CD3- IEL in non-celiac, celiac as well as refractory celiac disease