Activated T lymphocytes in the celiac lesion: Non‐proliferative activation (CD25) of CD4+ α/β cells in the lamina propria but proliferation (Ki‐67) of α/β and γ/δ cells in the epithelium

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Abstract
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) γ/δ+ 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 α 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 TcR5 showed that both TcR α/β+ CD8+ and TcR γδ+ (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 α/β+ CD8+ and TcR γδ+ IEL but non‐proliferative activation (lymphokine production?) of lamina propria CD4+ T cells.