Gluten stimulation of coeliac mucosa in vitro induces activation (CD25) of lamina propria CD4+ T cells and macrophages but no crypt-cell hyperplasia.
Jejunal biopsy specimens from 10 patients with treated coeliac disease and seven non-coeliac controls were challenged in vitro with peptic-tryptic gluten digest. Mucosal T cells were examined in situ by three-colour immunofluorescence staining for expression of the activation marker CD25 (the p55 alpha-chain of interleukin-2 receptor) and the nuclear proliferation marker revealed by monoclonal antibody Ki-67. Intraepithelial T cells expressed CD25 rarely whereas the proportion of activated lamina propria T cells increased (P < 0.002) from median 2.8% (cultured with 20% fetal calf serum alone for 24-48 h) to 10.0% after 24 h with gluten (n = 10; range 1.1-17.4%) and to 10.4% after 48 h (n = 7; range 1.4-17.5%). Such gluten-induced increase of CD25+ T cells was not observed in specimens from non-coeliac control subjects. Crypt-cell hyperplasia and T-cell proliferation (Ki-67+) were observed neither in the coeliac nor in the control mucosae after gluten stimulation. Three-colour staining combining a polyclonal antibody reagent to CD3 and a monoclonal antibody to CD25 with a monoclonal antibody to CD45R0, CD4, CD8, the p75 beta-chain of interleukin-2 receptor, integrin alpha E beta 7, or HLA-DR showed that most of the CD25+ T cells (> 90%) were CD4+CD8-, co-expressed CD45R0 and the p75 beta-chain, and often also the integrin alpha E beta 7 but not HLA-DR. In addition to these activated T cells, a dominating population of CD25+CD3-CD4+ subepithelial pan-HLA-class II+ macrophages (CD68+) with variable expression of the p75 beta-chain was often induced by gluten challenge.
Halstensen
T S
TS
Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), University of Oslo, National Hospital, Norway.
Scott
H
H
Fausa
O
O
Brandtzaeg
P
P
D000328:Adult; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002446:Celiac Disease / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005455:Fluorescent Antibody Technique; D005983:Glutens / Q000276:immunology*; D006801:Humans; D006965:Hyperplasia; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology*; D007583:Jejunum / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*
D001324:Autoantigens; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D015375:Receptors, Interleukin-2; D005983:Glutens