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CD8+ T cells are the most frequent T cell population in the immune cell compartment at the feto-maternal interface. Due to their cytotoxic potential, the presence of CD8+ T cells in the immune privileged pregnant uterus has raised considerable interest. Here, we review our current understanding of CD8+ T cell biology in the uterus of pregnant women and discuss this knowledge in relation to a recently published immune cell Atlas of human decidua. We describe how the expansion of CD8+ T cells with an effector memory phenotype often presenting markers of exhaustion is critical for a successful pregnancy, and host defense towards pathogens. Moreover, we review new evidence on the presence of long-lasting immunological memory to former pregnancies and discuss its impact on prospective pregnancy outcomes. The formation of fetal-specific memory CD8+ T cell subests in the uterus, in particular of tissue resident, and stem cell memory cells requires further investigation, but promises interesting results to come. Advancing the knowledge of CD8+ T cell biology in the pregnant uterus will be pivotal for understanding not only tissue-specific immune tolerance but also the etiology of complications during pregnancy, thus enabling preventive or therapeutic interventions in the future.

Cell populations in flow cytometry are typically identified via visual manual gating, a time-consuming and error-prone approach to select subpopulations based on expression of cellular markers. Batch processing can be used to automate the analysis of bimodally distributed data but underperforms with highly-variable or continuously-expressed markers. We developed a visual pattern recognition automated gating tool, BD ElastiGate Software (hereafter ElastiGate), to recapitulate the visual process of manual gating by automatically adjusting gates to capture local variability. ElastiGate converts histograms and two-dimensional plots into images, then uses elastic B-spline image registration to transform pre-gated training plot images and their gates to corresponding ungated target plot images, thereby adjusting for local variations. ElastiGate was validated with biologically relevant datasets in CAR-T cell manufacturing, tumor-infiltrating immunophenotyping, cytotoxicity assays (> 500 data files), and a high-dimensional dataset. Accuracy was evaluated against corresponding manually gated analysis using F1 score statistics. ElastiGate performed similarly to manual gating, with average F1 scores of > 0.9 across all gates. ElastiGate, accessible as a FlowJo Software plugin or in BD FACSuite Software, uses minimal training samples to automate gating while substantially reducing analysis time and outperforming existing 2D plot autogating solutions in F1 scores and ease of implementation.

Involved in immunity and reproduction, natural killer (NK) cells offer opportunities to develop new immunotherapies to treat infections and cancer or to alleviate pregnancy complications. Most current strategies use cytokines or antibodies to enhance NK-cell function, but none use ion channel modulators, which are widely used in clinical practice to treat hypertension, diabetes, epilepsy, and other conditions. Little is known about ion channels in NK cells. We show that , which codes for the Kir6.1 subunit of a certain type of ATP-sensitive potassium (K ) channel, is highly expressed in murine splenic and uterine NK cells compared to other K channels previously identified in NK cells. expression is highest in the most mature subset of splenic NK cells (CD27 /CD11b ) and in NKG2A or Ly49C/I educated uterine NK cells. Using patch clamping, we show that a subset of NK cells expresses a current sensitive to the Kir6.1 blocker PNU-37883A. does not participate in NK cell degranulation in response to tumor cells in vitro or rejection of tumor cells , or IFN-γ release. Transcriptomics show that genes previously implicated in NK cell development are amongst those differentially expressed in CD27 /CD11b NK cells deficient for . Indeed, we found that mice with NK-cell specific gene ablation have fewer CD27 /CD11b and KLRG-1 NK cells in the bone barrow and spleen. These results show that the K subunit Kir6.1 has a key role in NK-cell development.

Involved in immunity and reproduction, natural killer (NK) cells offer opportunities to develop new immunotherapies to treat infections and cancer or to alleviate pregnancy complications. Most current strategies use cytokines or antibodies to enhance NK-cell function, but none use ion channel modulators, which are widely used in clinical practice to treat hypertension, diabetes, epilepsy, and other conditions. Little is known about ion channels in NK cells. We show that which codes for the Kir6.1 subunit of a certain type of ATP-sensitive potassium (K ) channel, is highly expressed in murine splenic and uterine NK cells compared to other K channels previously identified in NK cells. expression is highest in the most mature subset of splenic NK cells (CD27 CD11b ) and in NKG2A or Ly49C/I educated uterine NK cells. Using patch clamping, we show that a subset of NK cells expresses a current sensitive to the Kir6.1 blocker PNU-37883A. does not participate in NK cell degranulation in response to tumor cells or rejection of tumor cells . Transcriptomics show that genes previously implicated in NK cell development are amongst those differentially expressed in CD27 CD11b NK cells deficient of . Indeed, we found that mice with NK-cell specific gene ablation have fewer CD11b CD27 and KLRG-1 NK cells in the bone barrow and spleen. These results show that the K subunit Kir6.1 has a key role in NK-cell development.

The Nordic Atlantic Cooperation (NORA) is an intergovernmental organization under the auspices of the Nordic Council of Ministers. The NORA region comprises Greenland, Iceland, Faroe Islands and western coastal areas of Norway. Historical, cultural and institutional links bind these nations together in multiple ways, and regional co-operation has in recent years become a focus of interest. This commentary addresses air medical services (AMSs) and available advanced hospital services in the 3 smallest NORA countries challenged sparse populations, hereafter referred to as the region. It seems likely that strengthened regional co-operation can help these countries to address common challenges within health care by exchanging know-how and best practices, pooling resources and improving the efficiency of care delivery. The 4 largest hospitals in the region, Dronning Ingrids Hospital in Nuuk (Greenland), Landspítali in Reykjavík and Sjúkrahúsið á Akureyri, (both in Iceland) and Landssjúkrahúsið Tórshavn on the Faroe Islands, have therefore undertaken the project Network for patient transport in the North-West Atlantic (in Danish: Netværk for patienttransport i Vest-Norden). The goal of the project, and of this article, is to exchange information and provide an overview of current AMSs and access to acute hospital care for severely ill or injured patients in the 3 participating countries. Of equal importance is the intention to highlight the need for increased regional co-operation to optimize use of limited resources in the provision of health care services.

The Nordic Atlantic Cooperation (NORA) is an intergovernmental organization under the auspices of the Nordic Council of Ministers. The NORA region comprises Greenland, Iceland, Faroe Islands and western coastal areas of Norway. Historical, cultural and institutional links bind these nations together in multiple ways, and regional co-operation has in recent years become a focus of interest. This commentary addresses air medical services (AMSs) and available advanced hospital services in the 3 smallest NORA countries challenged sparse populations, hereafter referred to as the region. It seems likely that strengthened regional co-operation can help these countries to address common challenges within health care by exchanging know-how and best practices, pooling resources and improving the efficiency of care delivery. The 4 largest hospitals in the region, Dronning Ingrids Hospital in Nuuk (Greenland), Landspítali in Reykjavík and Sjúkrahúsið á Akureyri, (both in Iceland) and Landssjúkrahúsið Tórshavn on the Faroe Islands, have therefore undertaken the project Network for patient transport in the North-West Atlantic (in Danish: Netværk for patienttransport i Vest-Norden). The goal of the project, and of this article, is to exchange information and provide an overview of current AMSs and access to acute hospital care for severely ill or injured patients in the 3 participating countries. Of equal importance is the intention to highlight the need for increased regional co-operation to optimize use of limited resources in the provision of health care services.