title: Dynamics of non-conventional intraepithelial lymphocytes-NK, NKT, and γδ T-in celiac disease: relationship with age, diet, and histopathology.
abstract: BACKGROUND
  Intraepithelial lymphocytes (IEL) are a heterogeneous population of lymphocytes raised in celiac disease (CD), whose role in CD pathogenesis remains to be defined.
  
  
  OBJECTIVE
  To investigate how the age of diagnosis, diet, and the severity of the histological lesions are related to the changes observed in unconventional IEL populations.
  
  
  METHODS
  Prospective analysis of 101 confirmed celiac patients from a single center, including 66 at diagnosis (45 children, 21 adults) and 112 non-celiac controls (12 children, 100 adults). IEL from duodenal biopsies were studied by six-color flow cytometry. The results were analyzed in relationship with age, diet (gluten intake), and histopathology (Marsh type).
  
  
  RESULTS
  In comparison with respective age controls, both children and adult patients showed duodenal intraepithelial lymphocytosis with significant differences in every single non-conventional IEL population: CD3+ TCR γδ, NK (CD3-, CD16+, CD56+), NKT (CD3+, CD161+, CD56+), and iNKT (CD3+ Vα24) (P < 0.001 for all). Gluten intake was not only directly associated with severe atrophy, but also with decreased percentages of NK (P = 0.02), NKT (P = 0.003), and iNKT (P = 0.03). Changes in iNKT and γδ IEL were more marked in celiac children compared with celiac adults (P = 0.02 and 0.01, respectively). In contrast, increased CD3+ TCR γδ were diet- and Marsh grade-independent.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Immunology, Complejo Hospitalario Universitario de León, Altos de Nava s/n, 24080, León, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Calleja
authors.forename: Santiago
authors.initials: S
authors.lastname: Vivas
authors.forename: María
authors.initials: M
authors.lastname: Santiuste
authors.forename: Laura
authors.initials: L
authors.lastname: Arias
authors.forename: Mercedes
authors.initials: M
authors.lastname: Hernando
authors.forename: Esther
authors.initials: E
authors.lastname: Nistal
authors.forename: Javier
authors.initials: J
authors.lastname: Casqueiro
authors.forename: Jose G
authors.initials: JG
authors.lastname: Ruiz de Morales
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002446:Celiac Disease / Q000276:immunology* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004032:Diet; D004386:Duodenum / Q000276:immunology*; D005260:Female; D005983:Glutens / Q000276:immunology; D006801:Humans; D007223:Infant; D007413:Intestinal Mucosa / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008218:Lymphocytosis / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D055815:Young Adult
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D005983:Glutens