Activated T lymphocytes in the celiac lesion: non-proliferative activation (CD25) of CD4+ alpha/beta cells in the lamina propria but proliferation (Ki-67) of alpha/beta and gamma/delta cells in the epithelium.
In order to identify any dominating subset of activated T cells in the celiac lesion, we examined CD3+, CD4+, CD8+ and T cell receptor (TcR) gamma/delta+ lymphocytes in jejunal cryosections from 25 patients with celiac disease and 10 controls by three-color immunofluorescence staining for expression of the nuclear proliferation marker detected by monoclonal antibody (mAb) Ki-67 and the p55 alpha chain of interleukin-2 receptor (CD25). mAb Ki-67+ intraepithelial lymphocytes (IEL) were exclusively observed in celiac patients. The median proportion of CD3+ IEL positive for Ki-67 increased from nil in controls to 4.5% in partly treated (range 0-19.0%; n = 10; p = < 0.05) and 12.8% in untreated celiac disease (range 4.0-30.7%; n = 15; p < 0.005). Only 1.5% of CD3+ subepithelial T cells expressed the Ki-67 marker in celiac disease (range 0-9.5%). Two- and three-color staining combining mAb to CD3 and Ki-67 with mAb to CD4, CD8 or TcR delta showed that both TcR alpha/beta+ CD8+ and TcR gamma/delta+ (but not CD4+) mucosal T cells proliferated in the epithelium. By contrast, CD25 were almost exclusively expressed on CD4+ T cells in the lamina propria. The percentage of CD25+ T cells increased significantly from 1.7% in controls (range 0-2.9%) to 7.5% in partly treated (range 0.8-17.8%, p < 0.002), and to 14.65% in untreated celiac disease (range 3.9-21%, p < 0.002). These results suggest that gluten ingestion in celiac disease induces proliferative activation of TcR alpha/beta+ CD8+ and TcR gamma/delta+ IEL but non-proliferative activation (lymphokine production?) of lamina propria CD4+ T cells.
Halstensen
T S
TS
Laboratory for Immunohistochemistry and Immunopathology (LIIPAT), University of Oslo, Rikshospitalet.
Brandtzaeg
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002446:Celiac Disease / Q000276:immunology* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004848:Epithelium / Q000276:immunology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007413:Intestinal Mucosa / Q000276:immunology*; D019394:Ki-67 Antigen; D008213:Lymphocyte Activation / Q000276:immunology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D009687:Nuclear Proteins / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2