Expression and T cell regulatory action of the PD-1 immune checkpoint in the ovary and fallopian tube.

PROBLEM: Immune cell trafficking and surveillance within the ovary and fallopian tube are thought to impact fertility and also tumorigenesis in those organs. However, little is known of how native cells of the ovary and fallopian tube interact with resident immune cells. Interaction of the Programmed Cell Death Protein-1 (PD-1/PDCD-1/CD279) checkpoint with PD-L1 is associated with downregulated immune response. We have begun to address the question of whether PD-1 ligand or its receptors (PD-L1/-L2) can regulate immune cell function in these tissues of the female reproductive tract. METHOD OF STUDY: PD-1 and ligand protein expression was evaluated in human ovary and fallopian tube specimens, the latter of which included stages of tubal cell transformation and early tumorigenesis. Ovarian expression analysis included the determination of the proteins in human follicular fluid (HFF) specimens collected during in vitro fertilization procedures. Finally, checkpoint bioactivity of HFF was determined by treatment of separately-isolated human T cells and the measurement of interferon gamma (IFNγ). RESULTS: We show that membrane bound and soluble variants of PD-1 and ligands are expressed by permanent constituent cell types of the human ovary and fallopian tube, including granulosa cells and oocytes. PD-1 and soluble ligands were present in HFF at bioactive levels that control T cell PD-1 activation and IFNγ production; full-length checkpoint proteins were found to be highly enriched in HFF exosome fractions. CONCLUSION: The detection of PD-1 checkpoint proteins in the human ovary and fallopian tube suggests that the pathway is involved in immunomodulation during folliculogenesis, the window of ovulation, and subsequent egg and embryo immune-privilege. Immunomodulatory action of receptor and ligands in HFF exosomes is suggestive of an acute checkpoint role during ovulation. This is the first study in the role of PD-1 checkpoint proteins in human tubo-ovarian specimens and the first examination of its potential regulatory action in the contexts of normal and assisted reproduction.

Species Composition, Temporal Abundance and Distribution of Insect Captures Inside and Outside Commercial Peanut Shelling Facilities.

Insect populations were studied within two commercial peanut shelling facilities located in the southeastern United States. Commercially available pheromone/kairomone-baited dome traps and pheromone-baited flight traps were deployed throughout processing and shipping portions of the shelling plants and serviced weekly over one year. Lasioderma serricorne, Tribolium castaneum, Typhaea stercorea, Carpophilus spp., Plodia interpunctella and Cadra cautella were the most common captures across locations. Lasioderma serricorne made up 87% and 88% of all captures in dome traps in plants one and two, respectively. While L. serricorne was not captured during the winter months in flight traps, it was captured with near 100% frequency in dome traps, suggesting that populations persisted throughout the year inside the facilities. Tribolium castaneum populations were active year round. Across insect species and trap type, temperature was a significant covariate for explaining variation in insect counts. After accounting for the effect of temperature, there were always more insects captured in the processing portions of the facilities compared to the shipping areas. A negative linear relationship was observed between captures of L. serricorne and T. castaneum and trap distance from in-shell peanuts entering the shelling facilities. Conversely, fungivores were more evenly distributed throughout all parts of the shelling plants. These data suggest that management efforts should be focused where in-shell peanuts enter to reduce breeding and harborage sites for grain feeding insects.

Communicatively Exploring Uncertainty Management of Parents of Children with Type 1 Diabetes.

Parents of children with type 1 diabetes (T1D) face uncertainty about the illness. This uncertainty can have negative health consequences for parents and their children. However, little is known about the types of uncertainty associated with T1D diagnosis and subsequent treatment and how this uncertainty is managed. Using uncertainty management theory (UMT) as a framework and 29 in-depth interviews with parents of children with T1D, this study found that parents experienced medical, social, and financial forms of uncertainty. Most parents viewed uncertainty negatively and sought to reduce it by seeking information, joining support groups, and turning to technology. However, some parents preferred uncertainty to the certainty of knowing their child had T1D and, at least initially, chose to maintain uncertainty about the disease by avoiding information. This study also provides practical outcomes that health-care providers can use to help parents of children with T1D reduce and manage uncertainty.