Deciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain.

Perivascular macrophages (pvMs) are associated with cerebral vasculature and mediate brain drainage and immune regulation. Here, using reporter mouse models, whole brain and section immunofluorescence, flow cytometry, and single cell RNA sequencing, besides the Lyve1+F4/80+CD206+CX3CR1+ pvMs, we identify a CX3CR1- pvM population that shares phagocytic functions and location. Furthermore, the brain parenchyma vasculature mostly hosts Lyve1+MHCII- pvMs with low to intermediate CD45 expression. Using the double Cx3cr1GFP x Cx3cr1-Cre;RosatdT reporter mice for finer mapping of the lineages, we establish that CD45lowCX3CR1- pvMs are derived from CX3CR1+ precursors and require PU.1 during their ontogeny. In parallel, results from the Cxcr4-CreErt2;Rosa26tdT lineage tracing model support a bone marrow-independent replenishment of all Lyve1+ pvMs in the adult mouse brain. Lastly, flow cytometry and 3D immunofluorescence analysis uncover increased percentage of pvMs following photothrombotic induced stroke. Our results thus show that the parenchymal pvM population is more heterogenous than previously described, and includes a CD45low and CX3CR1- pvM population.

Cross-talk between iNKT cells and CD8 T cells in the spleen requires the IL-4/CCL17 axis for the generation of short-lived effector cells.

Mounting an effective immune response relies critically on the coordinated interactions between adaptive and innate compartments. How and where immune cells from these different compartments interact is still poorly understood. Here, we demonstrate that the cross-talk between invariant natural killer T cells (iNKT) and CD8+ T cells in the spleen, essential for initiating productive immune responses, is biphasic and occurs at 2 distinct sites. Codelivery of antigen and adjuvant to antigen-presenting cells results in: 1) initial short-lived interactions (0 to 6 h), between CD8+ T cells, dendritic cells (DCs), and iNKT cells recruited outside the white pulp; 2) followed by long-lasting contacts (12 to 24 h) between iNKT cells, DCs, and CD8+ T cells occurring in a 3-way interaction profile within the white pulp. Both CXCR3 and CCR4 are essential to orchestrate this highly dynamic process and play nonredundant in T cell memory generation. While CXCR3 promotes memory T cells, CCR4 supports short-lived effector cell generation. We believe our work provides insights into the initiation of T cell responses in the spleen and their consequences for T cell differentiation.

Effect of pinaverium bromide on jejunal motility and colonic transit time in healthy humans.

Pinaverium bromide is a specific calcium channel blocker used in the treatment of irritable bowel syndrome (IBS) for its spasmolytic activity. The aim of the present study was to evaluate the effect of orally administered pinaverium bromide on jejunal motility and total and segmental colonic transit time in control subjects. Gastrointestinal studies were performed in 10 healthy volunteers (30 +/- 3 years), before and after a treatment phase of 14 days (150 mg/d). Jejunal motility was measured by prolonged manometry (14 h) and colonic transit time by a multiple ingestion, single marker technique. No significant modification of phase III of the migrating motor complexes was demonstrated. On the contrary, a significant (p < 0.01) but weak decrease of the frequency of contraction was found. Unlike previous studies, no decrease of total or segmental colonic transit time was demonstrated.

[Evaluation of 2 methods for detecting anti-DNA antibodies in collagen disease]. / Evaluation de deux méthodes de détection des anticorps anti-ADN natif dans les maladies du collagène.

An immunofluorescent technique using Crithidia luciliae (CL) has been developed to detect antibodies against native DNA, type them and determine their complement-fixing capacity. CL possess a kinetoplast containing double-stranded DNA that is not bound to histones: they are therefore a substrate well suited to the determination of antibodies against native DNA. When compared with a radioimmunoassay the technique displayed the same specificity and sensitivity. However, the correlation between clinical symptoms of SLE and anti-DNA antibody titer was better with the CL method than with radioimmunoassay. Determination of complement-fixing capacity and the type of immunoglobulins did not provide useful information. The CL method proved to be reliable, rapid and cheap.

[Minimal brain dysfunction. Our investigation of choreiform syndrome in children with MBD (author's transl)]. / Les dyskinésies dans notre expérience du dysfonctionnement cérébral minime (MBD).

It is the purpose of this communication to study statistical correlations between the different symptomes of MBD ; speech defect, dyslexia, hyperactivity, poor muscular control, give a school handicap for about 10 per cent of children, excluding cerebral palsy, sensorial trouble, or intellectual defect. The choreiforme syndrome is a systematic investigation in a group of 60 children selected with two symptomes of MBD. Choreiform movements are found in 48 per cent of our MBD patients (40 per cent of patients with hyperactivity and 50 per cent of patients with serious dyslexia).