Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity

A small proportion of multiple sclerosis (MS) patients develop new disease activity soon after starting anti-CD20 therapy. This activity does not recur with further dosing, possibly reflecting deeper depletion of CD20-expressing cells with repeat infusions. We assessed cellular immune profiles and their association with transient disease activity following anti-CD20 initiation as a window into relapsing disease biology. Peripheral blood mononuclear cells from independent discovery and validation cohorts of MS patients initiating ocrelizumab were assessed for phenotypic and functional profiles using multiparametric flow cytometry. Pretreatment CD20-expressing T cells, especially CD20dimCD8+ T cells with a highly inflammatory and central nervous system (CNS)-homing phenotype, were significantly inversely correlated with pretreatment MRI gadolinium-lesion counts, and also predictive of early disease activity observed after anti-CD20 initiation. Direct removal of pretreatment proinflammatory CD20dimCD8+ T cells had a greater contribution to treatment-associated changes in the CD8+ T cell pool than was the case for CD4+ T cells. Early disease activity following anti-CD20 initiation was not associated with reconstituting CD20dimCD8+ T cells, which were less proinflammatory compared with pretreatment. Similarly, this disease activity did not correlate with early reconstituting B cells, which were predominantly transitional CD19+CD24highCD38high with a more anti-inflammatory profile. We provide insights into the mode-of-action of anti-CD20 and highlight a potential role for CD20dimCD8+ T cells in MS relapse biology; their strong inverse correlation with both pretreatment and early posttreatment disease activity suggests that CD20-expressing CD8+ T cells leaving the circulation (possibly to the CNS) play a particularly early role in the immune cascades involved in relapse development

Efficient inverted polymer solar cells employing favourable molecular orientation

The improvement in the power conversion efficiency is a critical issue for polymer-based bulk-heterojunction solar cells (PSCs). Here, we show that high efficiencies of ~10% can be obtained by using a crystalline polymer, PNTz4T, in single-junction inverted cells with the thick active layer measuring ca. 300 nm. The improved performance is likely due to the large population of the polymer crystallites with the face-on orientation and the “favourable” distribution of edge-on and face-on crystallites along the film thickness, as revealed by in-depth studies of the blend films using grazing incidence wide angle X-ray diffraction, which results in the reduction of charge recombination and the efficient charge transport. These results underscore the great promise of PSCs, and raise hopes of achieving even higher efficiencies by materials development and control of molecular ordering