Celiac disease (CD) is a common inflammatory disorder of the small intestine which is triggered by ingested gluten proteins. Previous studies identified crucial steps in the development of celiac... Show moreCeliac disease (CD) is a common inflammatory disorder of the small intestine which is triggered by ingested gluten proteins. Previous studies identified crucial steps in the development of celiac disease and based on this knowledge, we propose a threshold model for the development of celiac disease which is described in chapter 1. It has also become clear that adult-onset celiac disease has a higher frequency of developing complications: refractory celiac disease (RCD) and enteropathy associated T cell lymphoma (EATL). About a decade ago, RCD was subdivided into RCD type I and RCD type II. This division was based on the respective absence or presence of an aberrant intraepithelial lymphocyte (IEL) population. These aberrant IELs were defined as surface TCR-CD3-CD4-CD8-CD7+CD03+, intracellular CD3+ cells and were identified as the missing link between regular IELs in uncomplicated celiac disease and lymphoma cells in EATL. The function and cellular origin of the aberrant IEL, however, remained unclear. The aim of this thesis was, therefore, to gain more insight in the phenotypical and functional characteristics of aberrant IELs as this might help to understand the events leading from uncomplicated CD to RCD II and gastrointestinal lymphoma. Show less