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Villitis of unknown etiology (VUE) is a prevalent inflammatory pathology of the placenta characterized by infiltration of maternal T cells and accumulation of fetal macrophages into chorionic villi. VUE is associated with a variety of adverse clinical outcomes, including fetal growth restriction and fetal demise. Evaluation of the phenotypic and functional differences between two immune cell types associated with this pathology, namely T cells and macrophages, was completed to gain a deeper understanding of the immuno-pathogenesis of VUE. GeoMx Digital Spatial Profiling was performed on placental tissue from 4 high grade VUE cases and 4 controls with no underlying pathology. Placental tissues were fluorescently labeled with CD3 and CD68 antibodies and oligo-conjugated antibodies against 48 protein targets. Overall, T cells in VUE exhibited upregulated markers of activation, memory, and antigen experience compared to controls and were altered based on placental location (villi vs. decidua). Additionally, villous macrophages in VUE upregulated costimulatory and major histocompatibility complex class I and II molecules compared to controls and macrophage subtypes in the decidua. Data herein provides new mechanistic insights into T cell and macrophage biology in VUE which contribute to this abnormal immune response to pregnancy. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD19+ CD5+ clonal B lymphocytes in the blood, bone marrow, and peripheral lymphoid organs. Treatment options for patients range from historical chemoimmunotherapy (CIT) to small molecule inhibitors targeting pro-survival pathways in leukemic B cells, such as the Bruton’s tyrosine kinase inhibitor ibrutinib (IBR). Using biobanked blood samples obtained pre-therapy and at standard response evaluation timepoints, we performed an in-depth evaluation of the blood innate and adaptive immune compartments between pentostatinbased CIT and IBR and looked for correlations with clinical sequelae. CD4+ conventional T cells and CD8+ cytotoxic T cells responded similarly to CIT and IBR, although exhaustion status differed. Both treatments dramatically increased the prevalence and functional status of monocyte, dendritic cell, and natural killer cell subsets. As expected, both regimens reduced clonal B cell levels however, we observed no substantial recovery of normal B cells. Although improvements in most immune subsets were observed with CIT and IBR at response evaluation, both patient groups remained susceptible to infections and secondary malignancies during the study. [ABSTRACT FROM AUTHOR]