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.


OBJECTIVE
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 Valpha24+ T cells by flow cytometry. iNK T cells were assessed by Valpha24 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 Valpha24 mRNA expression using relative PCR and for Valpha24+ T cells by immunofluorescence.


RESULTS
The mean numbers of circulating Valpha24+ 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, Valpha24 mRNA intestinal expression was reduced to 17% (p<0.001) by relative PCR and numbers of intestinal Valpha24+ T cells were 16% (p<0.01) of levels in control subjects.


CONCLUSIONS
We conclude that Valpha24+ 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.
Grose
R H
RH
Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Woodville Road, Woodville South, 5011, South Australia, Australia.
Cummins
A G
AG
Thompson
F M
FM
D000328:Adult; D000368:Aged; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis* / Q000235:genetics; D002446:Celiac Disease / Q000276:immunology*; D002478:Cells, Cultured; D004386:Duodenum / Q000276:immunology; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000032:analysis* / Q000235:genetics; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D018655:Lymphocyte Count; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; C045084:invariant chain; D015847:Interleukin-4