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 Vα24+ T cells by flow cytometry. iNK T cells were assessed by Vα24 and α-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 Vα24 mRNA expression using relative PCR and for Vα24+ T cells by immunofluorescence.
Results: The mean numbers of circulating Vα24+ 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, Vα24 mRNA intestinal expression was reduced to 17% (p<0.001) by relative PCR and numbers of intestinal Vα24+ T cells were 16% (p<0.01) of levels in control subjects.
Conclusions: We conclude that Vα24+ 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.
- αGalCer, α-galactosylceramide
- IFN, interferon
- IL, interleukin
- iNK T cell, invariant natural killer T cell
- coeliac disease
- NK T cells
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Published Online First 23 November 2006
Competing interests: None.
Ethics: This study was approved by the Human Ethics Committee of The Queen Elizabeth Hospital. The study was conducted according to the guidelines of the National Statement on Ethical Conduct in Research Involving Humans (1999) of the National Health and Medical Research Council of Australia.
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