FRI0002 IL-7 Induces T Cell-Dependent B Cell Activation in Patients with Primary Sjögren’s Syndrome and Its Expression in the Salivary Gland Correlates with Increased Number of Activated Lymphocytes

Background In patients with primary Sjögren’s syndrome (pSS), local T and B cell-driven inflammation contributes to destruction of exocrine glands associated with clinical symptoms of dryness. Recently increased IL-7 and IL7R expression in labial salivary glands (LSG) of pSS patients was documented. IL-7 causes T cell-dependent monocyte activation. Although there are indications that IL-7 affects the activity of developing human B-cells, the effect of IL-7 on mature B cell activation in human autoimmune diseases has not been reported previously. Because B cell activation plays a pivotal role in pSS pathology we investigated the capacity of IL-7 to induce (T cell-dependent) B-cell activation. Objectives To study the association of proliferating cells and interleukin-7 (IL-7) in the labial salivary gland (LSG) of pSS and non-Sjögren’s syndrome sicca (nSS-sicca) patients and the role of IL-7 in vitro to induce (T cell-dependent) B cell activation in vitro. Methods LSG from pSS and nSS-sicca patients were stained for Ki67 and correlated to the expression of IL-7. Peripheral blood mononuclear cells (PBMCs) and isolated CD4 T and B cells were analysed for ex vivo expression of the IL-7Rα. Analysis of activation markers (CD25, CD69 and HLA-DR) on CD4 T cells and B cells and proliferation of lymphocytes were determined after culture with IL-7 (3H-thymidine incorporation and Ki67 expression). Results An increased number of Ki67-proliferating cells per mm2 was found in the LSG of pSS as compared to nSS patients (pSS vs. nSS; 141±24 vs. 49±4, p<0.001), mainly confined to lymphocytic infiltrates. The number of these proliferating cells significantly correlated to the expression of IL-7 in LSG (r=0.643, p<0.001). In contrast to abundant IL-7R expression on CD4 T cells, CD19 B cells did not express IL-7Rα on their surface. In line with this IL-7 did not activate B cells directly, however in PBMC and CD4/CD19 co-cultures IL-7 significantly increased proliferation of and activation markers on both CD4 T cells (Ki67+ cells from 1.1±0.2% to 14.4±3.7%, p<0.01; CD25+ cells from 28.8±4.0% to 79.8±2.4%, p≤0.001; HLA-DR+ cells from 6.3±0.9% to 7.8±1.2%, p<0.05), and CD19 B cells (KI67+ cells from 1.9±0.3% to 4.1±0.9%, p<0.05; HLA-DR MFI from 282±110 to 375±135, p<0.05; mean increase of 37%). Conclusions To our knowledge, this is the first time that IL-7-induced T cell-dependent activation of mature B cells, which lack membrane expression of IL-7Rα, is demonstrated in humans. Together with the strong association of increased IL-7 expression and proliferating cells in the LSG of pSS, these results suggest that IL-7 is an important mediator in the immunopathology of pSS through activation of both T and indirectly B cells. Disclosure of Interest None Declared