title: Numbers of T cell receptor (TCR) alpha beta+ but not of TcR gamma delta+ intraepithelial lymphocytes correlate with the grade of villous atrophy in coeliac patients on a long term normal diet.
abstract: Numbers of T cell receptor (TcR) gamma delta+ and alpha beta+ intestinal lymphocytes were studied in 34 coeliac patients in respect of their diet and the grade of villous atrophy. Particular attention was given to a group of 21 patients with coeliac disease according to ESPGAN criteria who were on a well tolerated long term normal diet and in nine of whom the mucosa had returned to normal or nearly normal. A significant increase in TcR gamma delta+ cells was observed in the gut epithelium of coeliac patients compared with age matched controls, and this did not correlate with either the presence of gluten in the diet or with the grade of villous atrophy. Thus, numbers of TcR gamma delta+ intraepithelial lymphocytes (IEL) were considerably above the normal range in four of seven patients on a gluten free diet and in four of nine patients who had recovered a normal or nearly normal mucosa in spite of a normal diet. In contrast, numbers of intestinal TcR alpha beta+ cells varied with the stage of the disease. Their number was high in the epithelium of patients with active coeliac disease (n = 18) but significantly less in patients whose mucosa had returned to normal or nearly normal either after gluten free diet (n = 7) or in spite of a normal diet (n = 9). Immunohistochemical markers of intestinal mononuclear cell activation detected in active coeliac disease were either weakly expressed or absent in the latter patients. It is suggested that TcR alpha beta+ but not TcR gamma delta+ IEL are sensitised to gliadin in coeliac disease, and that only the former cells play a direct part in the pathogenesis of the villous atrophy. The normal counts of TcR alpha beta+ IEL and the absence of detectable mononuclear activation in the biopsy specimens of a few patients who have recovered clinical and histological tolerance to gluten sustains this hypothesis and also suggests that immunological tolerance to gluten may be acquired in a subgroup of coeliac patients. Hte appreciable increase in TcR gamma delta+ IEL observed in some of the latter patients, however, is similar to that observed in latent coeliac disease urging for their careful and prolonged follow up until the role of TcR gamma delta+ IEL in the pathogenesis of coeliac disease is elucidated.
authors.affiliation: Department of Paediatrics, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: T
authors.initials: T
authors.lastname: Kutlu
authors.forename: N
authors.initials: N
authors.lastname: Brousse
authors.forename: C
authors.initials: C
authors.lastname: Rambaud
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: J
authors.initials: J
authors.lastname: Schmitz
authors.forename: N
authors.initials: N
authors.lastname: Cerf-Bensussan
mesh_terms: D000293:Adolescent; D000328:Adult; D001284:Atrophy / Q000276:immunology; D002446:Celiac Disease / Q000178:diet therapy / Q000276:immunology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004032:Diet; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta