T-bet expression patterns in coeliac disease, cryptic and overt enteropathy-type T-cell lymphoma

Aims: To clarify the distribution and lineage allocation of T-bet-expressing cells in coeliac disease (CD) and in enteropathy-type T-cell lymphoma (ETTCL). The detection of elevated levels of interferon-gamma, interleukin-18 and the key regulator of Th1 helper immune response T-bet in CD biopsies led to the view that CD is the result of a Th1 response to gluten. It remains unknown whether T-bet is expressed in cryptic and overt ETTCL. Methods: Specimens from 20 patients with CD, five patients with cryptic and 10 patients with overt ETTCL were analysed by immunohistology employing single and double labellings for T-bet and CD4 or CD8 antigens. Results: In CD specimens nearly all intraepithelial CD8 cells and many CD4 cells in the lamina propria expressed T-bet. Cryptic ETTCL showed T-bet expression in the intraepithelial neoplastic cells while T-bet+ CD4 cells in the lamina propria were rare. Overt ETTCL showed T-bet expression in cases with non-anaplastic morphology. In addition, a proportion of bystander T cells expressed T-bet. Conclusions: Morphological evidence proves that while T-bet orchestrates a CD4- and CD8-based Th1 reaction in CD, its expression shifts to the neoplastic intraepithelial compartment of cryptic ETTCL and becomes absent or lost in anaplastic overt ETTCL.