Interleukin-7 and Toll-like receptor 7 induce synergistic B cell and T cell activation

A. Bikker, A.A. Kruize, K.M. Wurff-Jacobs, R.P. Peters, M. Kleinjan, F.A.M. Redegeld, W. de Jager, F.P.J.G. Lafeber, J.A.G. van Roon

Research output: Contribution to journalArticleAcademicpeer-review


OBJECTIVES: To investigate the potential synergy of IL-7-driven T cell-dependent and TLR7-mediated B cell activation and to assess the additive effects of monocyte/macrophages in this respect. METHODS: Isolated CD19 B cells and CD4 T cells from healthy donors were co-cultured with TLR7 agonist (TLR7A, Gardiquimod), IL-7, or their combination with or without CD14 monocytes/macrophages (T/B/mono; 1 : 1 : 0,1). Proliferation was measured using 3H-thymidine incorporation and Ki67 expression. Activation marker (CD19, HLA-DR, CD25) expression was measured by FACS analysis. Immunoglobulins were measured by ELISA and release of cytokines was measured by Luminex assay. RESULTS: TLR7-induced B cell activation was not associated with T cell activation. IL-7-induced T cell activation alone and together with TLR7A synergistically increased numbers of both proliferating (Ki67+) B cells and T cells, which was further increased in the presence of monocytes/macrophages. This was associated by up regulation of activation markers on B cells and T cells. Additive or synergistic induction of production of immunoglobulins by TLR7 and IL-7 was associated by synergistic induction of T cell cytokines (IFNgamma, IL-17A, IL-22), which was only evident in the presence of monocytes/macrophages. CONCLUSIONS: IL-7-induced CD4 T cell activation and TLR7-induced B cell activation synergistically induce T helper cell cytokine and B cell immunoglobulin production, which is critically dependent on monocytes/macrophages. Our results indicate that previously described increased expression of IL-7 and TLR7 together with increased numbers of macrophages at sites of inflammation in autoimmune diseases like RA and pSS significantly contributes to enhanced lymphocyte activation.
Original languageEnglish
Article numbere94756
Number of pages9
JournalPLoS One
Issue number4
Publication statusPublished - 2014


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