The intestinal expansion of TCRγδ+ and disappearance of IL4+ T cells suggest their involvement in the evolution from potential to overt celiac disease

Abstract

Celiac disease (CD) is characterized by a spectrum of intestinal inflammatory lesions. Most patients have villous atrophy (overt-CD), while others have a morphologically normal mucosa, despite the presence of CD-specific autoantibodies (potential-CD). As the mechanism responsible for villous atrophy is not completely elucidated, we investigated biomarkers specific for the different celiac lesions. Phenotype and cytokine production of intestinal mucosa cells were analyzed by flow cytometry in gut biopsies of children with overt- or potential-CD and in healthy controls. Density of TCRγδ⁺ T cells was found markedly enhanced in intestinal mucosa of children with overt-CD compared to potential-CD or controls. By contrast, very few IL4⁺ T cells infiltrated the mucosa with villous atrophy compared to morphologically normal mucosa. IL4⁺ T cells were classical CD4⁺ T-helper cells (CD161^- ), producing or not IFN-γ, and negative for IL17A. Our study demonstrated that the transition to villous atrophy in CD patients is characterized by increased density of TCRγδ⁺ T cells, and concomitant disappearance of IL4⁺ cells. These findings suggest that immunomodulatory mechanisms are active in potential-CD to counteract the inflammatory cascade responsible of villous atrophy. Further studies are required to validate the use of IL4⁺ and TCRγδ⁺ T cells as biomarkers of the different CD forms.

Keywords: Celiac disease; Cytokines; Flow cytometry; Intestinal TCRγδ+ T cells; Mucosal immunology.