Dynamics of Non-conventional Intraepithelial Lymphocytes—NK, NKT, and γδ T—in Celiac Disease: Relationship with Age, Diet, and Histopathology

Abstract

The typical phenotypical profile of intraepithelial lymphocytosis in untreated pediatric and adult celiacs consists of increased CD3+ TCR γδ populations with decreased NK, NKT, and iNKT cells. NK, NKT, and iNKT IEL, but not γδ IEL, are dynamic populations associated with diet, age, and histopathology.

The composition and differentiation potential of the duodenal intraepithelial innate lymphocyte compartment is altered in coeliac disease

“…CD, for example, is characterised by an expansion of intraepithelial T lymphocytes (T-IEL) and a reduction in CD3-negative or innate IELs 3 7–9 16 17 36. Our results suggest that local differentiation of T cells from Lin- innate IELs may contribute to this phenomenon.…”

“…As the size of the innate IEL population as a whole is decreased in patients with CD compared with non-coeliac controls,3 7–9 16 17 and as children show higher frequencies of Lin − CD127 − IEL than adults,13 we considered the possibility that the composition of the innate IEL compartment is influenced by age and disease. We therefore determined the relative abundance of the IEL subpopulations in the fetal intestine, as well as duodenal biopsies from children and adults without CD, children and adults with CD, and adults with RCDII.…”

“…In active CD the number of IELs is greatly increased (>20 per 100 enterocytes). While TCRαβ and TCRγδ T cell numbers are increased, the innate IEL frequencies are reduced dramatically 3 7–9 16 17. Adherence to a gluten-free diet usually restores the TCRαβ T cell frequencies to normal, but the TCRγδ T cell frequencies remain increased 18 19.…”

Age-related differences in celiac disease: Specific characteristics of adult presentation

“…The function of γδ IELs is not known, but they could have a regulatory role in the immune response [29] . This would explain their relationship with the degree of villous atrophy both in children and in adults [30] . Another characteristic population is CD3-, which is inversely related to age.…”

Immunopathology of Celiac Disease

“…TCRγδ + IELs are increased in the gut epithelium of active CD patients (Halstensen et al, 1989;Spencer et al, 1989) and intriguingly persist in patients on a GFD (Calleja et al, 2011;Jarvinen et al, 2003;Kutlu et al, 1993). This expansion of TCRγδ + IELs is a hallmark of CD, yet we know little about the mechanisms underlying their expansion and their role in CD pathogenesis.…”