Primary B-Cell Deficiencies Reveal a Link between Human IL-17-Producing CD4 T-Cell Homeostasis and B-Cell Differentiation

IL-17 is a pro-inflammatory cytokine implicated in autoimmune and inflammatory conditions. The development/survival of IL-17-producing CD4 T cells (Th17) share critical cues with B-cell differentiation and the circulating follicular T helper subset was recently shown to be enriched in Th17 cells able to help B-cell differentiation. We investigated a putative link between Th17-cell homeostasis and B cells by studying the Th17-cell compartment in primary B-cell immunodeficiencies. Common Variable Immunodeficiency Disorders (CVID), defined by defects in B-cell differentiation into plasma and memory B cells, are frequently associated with autoimmune and inflammatory manifestations but we found no relationship between these and Th17-cell frequency. In fact, CVID patients showed a decrease in Th17-cell frequency in parallel with the expansion of activated non-differentiated B cells (CD21lowCD38low). Moreover, Congenital Agammaglobulinemia patients, lacking B cells due to impaired early B-cell development, had a severe reduction of circulating Th17 cells. Finally, we found a direct correlation in healthy individuals between circulating Th17-cell frequency and both switched-memory B cells and serum BAFF levels, a crucial cytokine for B-cell survival. Overall, our data support a relationship between Th17-cell homeostasis and B-cell maturation, with implications for the understanding of the pathogenesis of inflammatory/autoimmune diseases and the physiology of B-cell depleting therapies

Immune Responses Elicited in Tertiary Lymphoid Tissues Display Distinctive Features

During chronic inflammation, immune effectors progressively organize themselves into a functional tertiary lymphoid tissue (TLT) within the targeted organ. TLT has been observed in a wide range of chronic inflammatory conditions but its pathophysiological significance remains unknown. We used the rat aortic interposition model in which a TLT has been evidenced in the adventitia of chronically rejected allografts one month after transplantation. The immune responses elicited in adventitial TLT and those taking place in spleen and draining lymph nodes (LN) were compared in terms of antibody production, T cell activation and repertoire perturbations. The anti-MHC humoral response was more intense and more diverse in TLT. This difference was associated with an increased percentage of activated CD4+ T cells and a symmetric reduction of regulatory T cell subsets. Moreover, TCR repertoire perturbations in TLT were not only increased and different from the common pattern observed in spleen and LN but also “stochastic,” since each recipient displayed a specific pattern. We propose that the abnormal activation of CD4+ T cells promotes the development of an exaggerated pathogenic immune humoral response in TLT. Preliminary findings suggest that this phenomenon i) is due to a defective immune regulation in this non-professional inflammatory-induced lymphoid tissue, and ii) also occurs in human chronically rejected grafts

WOOD-ADHESIVE INTERFACE CHARACTERIZATION AND MODELING IN ENGINEERED WOOD FLOORING

Adhesive films used in layered wood-based composites have a significant impact on moisture movement and must be considered in models of such products. The objective of this study was to characterize the wood-adhesive interface and determine its impact on the hygromechanical behavior of engineered wood flooring (EWF). The radial water vapor diffusion coefficient and the coefficients of moisture expansion were determined for sugar maple wood, crosslinked polyviny1 acetate adhesive film (XPVAc), and the wood-adhesive interface. Sugar maple wood had the highest diffusion coefficient at 1.66 x 10-11 m2 · s-1 followed by the wood-adhesive interface at 5.73 x 10-12 m2 · s-1, and the free XPVAc film at 4.18 x 10-12 m2 · s-1. The coefficient of tangential moisture expansion of the sugar maple wood-adhesive interface was found to be 4 x 10-3 (%MC)-1 compared with 3 x 10-3 (%MC)-1 for sugar maple wood in the tangential direction, and 3 x 10-3 (%MC)-1 for the XPVAc film. Finite element modeling of EWF hygromechanical cupping did not show significant differences between hygromechanical cupping calculated with and without interface effects

Impact of short term use of interdialytic 60% ethanol lock solution on tunneled silicone catheter dysfunction.

International audienceINTRODUCTION: Ethanol lock (EL) is used to reduce catheter infections, but its impact on dialysis catheter dysfunction has not been studied. METHODS: We analyzed the rate of dialysis silicone catheter dysfunction after an interdialytic 60% EL in an open prospective controlled non crossover cohort study, with each patient being his or her own control. The study was divided into three consecutive 2-week periods: the pre- and post-intervention periods, in which interdialytic standard locks (SL) were used, and the intervention period, in which one EL was instilled during the first week, and two consecutively in the second week. We analyzed the rate of catheter dysfunction (exchange, use of fibrinolytic, reversing the lines, difficulty in instilling or withdrawing fluid) after EL or SL. RESULTS: In 30 patients, 90 EL were instilled. The rate of catheter dysfunction increased during the EL period (2 - 13%, p < 0.001), and between the two consecutive dialysis sessions before and after EL (p < 0.05). It decreased between the two consecutive dialysis sessions after EL and the following dialysis session after an SL (p < 0.05). No catheter was removed. The urea reduction ratio did not differ in dialysis after an SL and after an EL (0.77 vs. 0.73, p = 0.17). CONCLUSION: Short term EL is associated with a transient increase in catheter dysfunction, without resulting in catheter removal or decreasing dialysis efficiency