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

Abstract

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. 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. 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. 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.