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After resolution of infection, T cells differentiate into long-lived memory cells that recirculate through secondary lymphoid organs or establish residence in tissues. In contrast to CD8+ tissue-resident memory T cells (TRM), the developmental origins and transcriptional regulation of CD4+ TRM remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles of CD4+ TRM in the small intestine (SI) responding to acute viral infection, revealing a shared gene expression program and chromatin accessibility profile with circulating TH1 and the progressive acquisition of a mature TRM program. Single-cell RNA sequencing identified heterogeneity among established CD4+ TRM, which were predominantly located in the lamina propria, and revealed a population of cells that coexpressed both effector- and memory-associated genes, including the transcriptional regulators Blimp1, Id2, and Bcl6. TH1-associated Blimp1 and Id2 and TFH-associated Bcl6 were required for early TRM formation and development of a mature TRM population in the SI. These results demonstrate a developmental relationship between TH1 effector cells and the establishment of early TRM, as well as highlighted differences in CD4+ versus CD8+ TRM populations, providing insights into the mechanisms underlying the origins, differentiation, and persistence of CD4+ TRM in response to viral infection.

After resolution of infection, T cells differentiate into long-lived memory cells that recirculate through secondary lymphoid organs or establish residence in tissues. In contrast to CD8+ tissue-resident memory T cells (TRM), the developmental origins and transcriptional regulation of CD4+ TRM remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles of CD4+ TRM in the small intestine (SI) responding to acute viral infection, revealing a shared gene expression program and chromatin accessibility profile with circulating TH1 and the progressive acquisition of a mature TRM program. Single-cell RNA sequencing identified heterogeneity among established CD4+ TRM, which were predominantly located in the lamina propria, and revealed a population of cells that coexpressed both effector- and memory-associated genes, including the transcriptional regulators Blimp1, Id2, and Bcl6. TH1-associated Blimp1 and Id2 and TFH-associated Bcl6 were required for early TRM formation and development of a mature TRM population in the SI. These results demonstrate a developmental relationship between TH1 effector cells and the establishment of early TRM, as well as highlighted differences in CD4+ versus CD8+ TRM populations, providing insights into the mechanisms underlying the origins, differentiation, and persistence of CD4+ TRM in response to viral infection. Committed to memory: Long-lived CD4+ tissue resident memory T cells (TRM) are a crucial component of immune memory, yet their origin and transcriptional regulation are not well understood. Nguyen et al. studied the differentiation of CD4+ T cells in the small intestine (SI) after acute LCMV infection. CD4+ TRM cells localized to the lamina propria; were phenotypically, transcriptionally, and epigenetically related to TH1 cells; and acquired a mature TRM program over time. A subset of CD4+ TRM co-expressed the antagonistic transcription factors Bcl6 and Blimp1, which, along with Id2, were required to establish TRM. These findings highlight that CD4+ TRM have a hybrid transcriptional program with expression of effector and memory genes and suggest that in viral infection, circulating TH1 cells are developmental precursors of SI CD4+ TRM. —HMI [ABSTRACT FROM AUTHOR]

Purpose: Following an assessment of safe sleep practices (SSP) and nurses' safe sleep knowledge in a Neonatal Intensive Care Unit (NICU), an evidence-based 2-part safe sleep program including nurse education and the use of safe sleep cards was developed in an attempt to increase SSP. Design: A quality improvement project with time-series methodology, including observational and survey data collection. Sample: To assess SSP, sleep environment audits were completed pre- (N = 48) and post- safe sleep program (N = 44). To assess nurses' safe sleep knowledge, a safe sleep questionnaire was distributed pre-education (N = 48) and post-education (N = 23). Main Outcome Variable: The change in SSP (ΔSSP) following safe sleep program implementation and change in nurses' safe sleep knowledge (ΔKnowledge) following education. Results: SSP increased from 25 percent to 61 percent compliance, and nurses' knowledge scores increased from 83 percent to 97 percent. [ABSTRACT FROM AUTHOR]

Immortalized human lymphoblastoid cell lines have been used to demonstrate that it is possible to use an in vitro model system to identify genetic factors that affect responses to xenobiotics. To extend the application of such studies to investigative toxicology by assessing interindividual and population-wide variability and heritability of chemical-induced toxicity phenotypes, we have used cell lines from the Centre d'Etude du Polymorphisme Humain (CEPH) trios assembled by the HapMap Consortium. Our goal is to aid in the development of predictive in vitro genetics-anchored models of chemical-induced toxicity. Cell lines from the CEPH trios were exposed to three concentrations of 14 environmental chemicals. We assessed ATP production and caspase-3/7 activity 24 h after treatment. Replicate analyses were used to evaluate experimental variability and classify responses. We show that variability of response across the cell lines exists for some, but not all, chemicals, with perfluorooctanoic acid (PFOA) and phenobarbital eliciting the greatest degree of interindividual variability. Although the data for the chemicals used here do not show evidence for broad-sense heritability of toxicity response phenotypes, substantial cell line variation was found, and candidate genetic factors contributing to the variability in response to PFOA were investigated using genome-wide association analysis. The approach of screening chemicals for toxicity in a genetically defined yet diverse in vitro human cell-based system is potentially useful for identification of chemicals that may pose a highest risk, the extent of within-species variability in the population, and genetic loci of interest that potentially contribute to chemical susceptibility. [ABSTRACT FROM PUBLISHER]

The article reports on under served U.S. communities of color which do not have access to safe and clean water and sewer infrastructure and other services and discusses the factors which have led to the lack of services. A research and community organizing initiative which was developed to address water and sanitation concerns in a community in Chapel Hill, North Carolina is discussed. Strategies for communities experiencing similar problems are examined.