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खुला एक्सेस

अमूर्त

Type 1 Diabetic Children and Siblings Share a Decrease in Dendritic Cell and Monocyte Numbers but are Differentiated by Expansion of CD4+T Cells Expressing IL-17

Andrew Wilkinson, Lei Bian, Dalia Khalil, Kristen Gibbons, Pooi-Fong Wong, Derek N.J. Hart, Mark Harris, Andrew Cotterill and Slavica Vuckovic

Type 1 diabetes (T1D) is an autoimmune disease characterised by multiple defects of immune cells which allow the expansion of pathogenic β cell-specific T effector cells and subsequent T1D development. We performed immunomonitoring assays on blood immune cells in T1D children, their siblings and controls with the supposition that the results would elucidate the sequence of abnormalities in peripheral immune cells leading to the progression of autoimmunity from non-diabetic siblings to diabetic children. We assessed myeloid dendritic cell (MDC), plasmacytoid (P)DC, monocyte, CD4⁺T and CD8⁺T cell compartments, and cytokine expression in CD4⁺T cells and CD8⁺T cells, by polychromatic flow cytometry in erythrocyte-lysed fresh blood. The numbers of CD16⁺MDC, PDC and CD16⁺ monocytes were similarly decreased in diabetic children and their siblings. Whereas the numbers of CD16^-CD141^-MDC, CD16^-CD141⁺MDC, CD16^- monocytes, T naïve (CD45RO^-CD62L⁺), T central memory (CD45RO⁺CD62L⁺), T effector memory (CD45RO⁺CD62L^-), T terminally-differentiated effector (CD45ROCD62L^-) and T regulatory cells (CD4⁺CD25⁺127lo/^- or CD4⁺Foxp3⁺ cells) were not affected in diabetic children or their siblings. Furthermore, analysis of cytokine expression in CD4⁺T cells and CD8⁺T cell revealed an increased proportion of CD4⁺T cells expressing IL^-17, differentiating diabetic children from their non-diabetic siblings. Our data suggest that diabetic children and their siblings suffer a considerable reduction of blood immune cells involving CD16⁺MDC, PDC and CD16⁺ monocytes that may result from shared genetic or environmental factors. However, this reduction of blood immune cells requires combination with the proinflammatory cytokine IL-17 to allow disease expression in diabetic children.