Deficiency of invariant natural killer T cells in coeliac disease

Background: Immunoregulatory invariant natural killer (iNK) T cells rapidly produce interleukin (IL)-4 and other cytokines that suppress a Th1 response and are deficient in some autoimmune diseases. Aim: The aim of this study was to investigate any deficiency of iNK T cells in coeliac disease. Methods: Blood was collected from 86 subjects with coeliac disease and from 152 healthy control subjects for investigation of V alpha 24+ T cells by flow cytometry. iNK T cells were assessed by V alpha 24 and alpha-galactosylceramide/CD1d tetramer markers in 23 normal controls and 13 subjects with coeliac disease. Intracellular IL-4 was measured after anti-CD3 antibody stimulation. Duodenal biopsies were obtained in a subgroup of subjects with coeliac disease and control subjects for V alpha 24 mRNA expression using relative PCR and for V alpha 24+ T cells by immunofluorescence. Results: The mean numbers of circulating V alpha 24+ T cells and iNK T cells in coeliac disease were 27% (p < 0.001) and 16% (p < 0.001), respectively, of levels in control subjects. After in vitro anti-CD3 stimulation, numbers of IL-4+ producing iNK T cells from subjects with coeliac disease were unchanged but increased by 21% in control subjects. In subjects with coeliac disease, V alpha 24 mRNA intestinal expression was reduced to 17% (p < 0.001) by relative PCR and numbers of intestinal V alpha 24+ T cells were 16% (p < 0.01) of levels in control subjects. Conclusions: We conclude that V alpha a24+ T cells and iNK T cells are deficient in coeliac disease. We speculate that this deficiency could contribute to the failure of immunological oral tolerance that seems to underlie this disease.