Blocking immunosuppression by human Tregs in vivo with antibodies targeting integrin αVß8.

Human regulatory T cells (Tregs) suppress other T cells by converting the latent, inactive form of TGF-ß1 into active TGF-ß1. In Tregs, TGF-ß1 activation requires GARP, a transmembrane protein that binds and presents latent TGF-ß1 on the surface of Tregs stimulated through their T cell receptor. However, GARP is not sufficient because transduction of GARP in non-Treg T cells does not induce active TGF-ß1 production. RGD-binding integrins were shown to activate TGF-ß1 in several non-T cell types. Here we show that αVß8 dimers are present on stimulated human Tregs but not in other T cells, and that antibodies against αV or ß8 subunits block TGF-ß1 activation in vitro. We also show that αV and ß8 interact with GARP/latent TGF-ß1 complexes in human Tregs. Finally, a blocking antibody against ß8 inhibited immunosuppression by human Tregs in a model of xenogeneic graft-vs.-host disease induced by the transfer of human T cells in immunodeficient mice. These results show that TGF-ß1 activation on the surface of human Tregs implies an interaction between the integrin αVß8 and GARP/latent TGF-ß1 complexes. Immunosuppression by human Tregs can be inhibited by antibodies against GARP or against the integrin ß8 subunit. Such antibodies may prove beneficial against cancer or chronic infections.

Annual variation in neustonic micro- and meso-plastic particles and zooplankton in the Bay of Calvi (Mediterranean-Corsica).

The annual variation in neustonic plastic particles and zooplankton was studied in the Bay of Calvi (Corsica) between 30 August 2011 and 7 August 2012. Plastic particles were classified into three size classes, small microplastics (0.2-2mm), large microplastics (2-5mm) and mesoplastics (5-10mm). 74% of the 38 samples contained plastic particles of varying composition: e.g. filaments, polystyrene, thin plastic films. An average concentration of 6.2 particles/100 m(2) was observed. The highest abundance values (69 particles/100 m(2)) observed occurred during periods of low offshore wind conditions. These values rose in the same order of magnitude as in previous studies in the North Western Mediterranean. The relationships between the abundance values of the size classes between zooplankton and plastic particles were then examined. The ratio for the intermediate size class (2-5mm) reached 2.73. This would suggest a potential confusion for predators regarding planktonic prey of this size class.

Neustonic microplastic and zooplankton in the North Western Mediterranean Sea.

Neustonic microplastic and zooplankton abundance was determined in the North Western Mediterranean Sea during a summer cruise between July 9th and August 6th 2010, with a break between July 22 th and 25th due to a strong wind event. Ninety percent of the 40 stations contained microplastic particles (size 0.3-5mm) of various compositions: e.g., filaments, polystyrene, thin plastic films. An average concentration of 0.116 particles/m(2) was observed. The highest abundances (>0.36 particles/m(2)) were observed in shelf stations. The neustonic plastic particles concentrations were 5 times higher before than after the strong wind event which increased the mixing and the vertical repartition of plastic particles in the upper layers of the water column. The values rise in the same order of magnitude than in the North Pacific Gyre. The average ratio between microplastics and mesozooplankton weights was 0.5 for the whole survey and might induce a potential confusion for zooplankton feeders.