Infusion of a simianized anti-αβ mAb (Rh-αβ) just before and following SIV infection protected rhesus macaques from developing AIDS and partially from vaginal SIV acquisition. Recently, short-term treatment with Rh-αβ in combination with cART was found to lead to prolonged viral suppression after withdrawal of all therapeutic interventions. The humanized form of Rh-αβ, vedolizumab, is a highly effective treatment for inflammatory bowel disease. To clarify the mechanism of action of Rh-αβ, naive macaques were infused with Rh-αβ and sampled in blood and tissues before and after treatment to monitor several immune cell subsets. In blood, Rh-αβ increased the CD4 and CD8 T cell counts, but not B cell counts, and preferentially increased CCR6 subsets while decreasing CD103 and CD69 lymphocytes. In mucosal tissues, surprisingly, Rh-αβ did not impact integrin α cells, but decreased the frequencies of CCR6 and CD69 CD4 T cells and, in the gut, Rh-αβ transiently decreased the frequency of memory and IgA B cells. In summary, even in the absence of inflammation, Rh-αβ impacted selected immune cell subsets in different tissues. These data provide new insights into the mechanisms by which Rh-αβ may mediate its effect in SIV-infected macaques with implications for understanding the effect of treatment with vedolizumab in patients with inflammatory bowel disease.

Background Nonvalvular atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with the prothrombotic state. Circulating microparticles (cMPs) are membrane vesicles that are shed from many cell types in response to cell activation and cell apoptosis. Several studies reported that cMPs may play a role in the hypercoagulable state that can be observed in patients with AF. The aim of this study was to determine the levels of total cMPs and characterize their cellular origins in AF patients. Methods Atotal of 66 AF patients and 33 healthy controls were enrolled. This study investigated total cMP levels and their cellular origin in AF patients using polychromatic flow cytometry. Results AF patients had significantly higher levels of total cMPs (median 36.38, interquartile range [IQR] 21.16‐68.50 × 10 5 counts/mL vs median 15.21, IQR 9.91‐30.86 × 10 5 counts/mL; P = 0.004), platelet‐derived MPs (PMPs) (median 10.61, IQR 6.55‐18.04 × 10 5 counts/mL vs median 7.83, IQR 4.44‐10.26 × 10/mL; P = 0.009), and endothelial‐derived MPs (EMPs CD31+ CD41−) (median 2.94, IQR 1.78‐0.60 × 10 5 counts/mL vs median 1.16, IQR 0.71‐2.30 × 10 5 counts/mL; P = 0.001) than healthy controls after adjusting for potential confounders. Phosphatidylserine positive MP (PS + MP) levels were similar compared between AF patients and healthy controls. Conclusion The results of this study revealed a marked increase in total cMP levels, and evidence of elevated endothelial damage and platelet activation, as demonstrated by increased PMP and EMP levels, in AF patients. Additional study is needed to further elucidate the role of cMPs (PMPs and EMPs) in the pathophysiology of and the complications associated with AF.