KDM6B-dependent chromatin remodeling underpins effective virus-specific CD8 T cell differentiation.

Naive CD8 T cell activation results in an autonomous program of cellular proliferation and differentiation. However, the mechanisms that underpin this process are unclear. Here, we profile genome-wide changes in chromatin accessibility, gene transcription, and the deposition of a key chromatin modification (H3K27me3) early after naive CD8 T cell activation.

Evaluation of Ethics Curricula and Faculty in Accredited Undergraduate Radiologic Technology Programs.

Purpose: To investigate the state of ethics curricula in accredited undergraduate radiologic technology programs.

Methods: A causal-comparative research design was used to collect and analyze data about faculty degrees, their knowledge of the Realm-Individual Process-Situation (RIPS) Model of Ethical Decision-Making, the degree level offered, and the ethics curriculum. Postprimary certification programs and applicant programs for accreditation were excluded.

Post-thrombectomy intracranial blooming artifact.

Mechanical thrombectomy is a procedure used for the treatment of acute ischemic stroke in patients with large vessel occlusions. Usually with a low complication rate, we present a case with a complication post-thrombectomy not previously described in the literature noted on imaging as "blooming artifact".

Early T-BET Expression Ensures an Appropriate CD8 Lineage-Specific Transcriptional Landscape after Influenza A Virus Infection.

Virus infection triggers large-scale changes in the phenotype and function of naive CD8 T cells, resulting in the generation of effector and memory T cells that are then critical for immune clearance. The T-BOX family of transcription factors (TFs) are known to play a key role in T cell differentiation, with mice deficient for the TF T-BET (encoded by unable to generate optimal virus-specific effector responses. Although the importance of T-BET in directing optimal virus-specific T cell responses is accepted, the precise timing and molecular mechanism of action remains unclear.

Peripheral and systemic antigens elicit an expandable pool of resident memory CD8 T cells in the bone marrow.

BM has been put forward as a major reservoir for memory CD8  T cells. In order to fulfill that function, BM should "store" memory CD8 T cells, which in biological terms would require these "stored" memory cells to be in disequilibrium with the circulatory pool. This issue is a matter of ongoing debate.

CD4 T help promotes influenza virus-specific CD8 T cell memory by limiting metabolic dysfunction.

There is continued interest in developing novel vaccine strategies that induce establish optimal CD8 cytotoxic T lymphocyte (CTL) memory for pathogens like the influenza A viruses (IAVs), where the recall of IAV-specific T cell immunity is able to protect against serologically distinct IAV infection. While it is well established that CD4 T cell help is required for optimal CTL responses and the establishment of memory, when and how CD4 T cell help contributes to determining the ideal memory phenotype remains unclear. We assessed the quality of IAV-specific CD8 T cell memory established in the presence or absence of a concurrent CD4 T cell response.

CD8 T Cell Activation Leads to Constitutive Formation of Liver Tissue-Resident Memory T Cells that Seed a Large and Flexible Niche in the Liver.

Liver tissue-resident memory T (Trm) cells migrate throughout the sinusoids and are capable of protecting against malaria sporozoite challenge. To gain an understanding of liver Trm cell development, we examined various conditions for their formation. Although liver Trm cells were found in naive mice, their presence was dictated by antigen specificity and required IL-15.

Mouse Norovirus Infection Reduces the Surface Expression of Major Histocompatibility Complex Class I Proteins and Inhibits CD8 T Cell Recognition and Activation.

Human noroviruses are highly infectious single-stranded RNA (ssRNA) viruses and the major cause of nonbacterial gastroenteritis worldwide. With the discovery of murine norovirus (MNV) and the introduction of an effective model for norovirus infection and replication, knowledge about infection mechanisms and their impact on the host immune response has progressed. A major player in the immune response against viral infections is the group of major histocompatibility complex (MHC) class I proteins, which present viral antigen to immune cells.

Phospholipase A2 activity during the replication cycle of the flavivirus West Nile virus.

Positive-sense RNA virus intracellular replication is intimately associated with membrane platforms that are derived from host organelles and comprised of distinct lipid composition. For flaviviruses, such as West Nile virus strain Kunjin virus (WNVKUN) we have observed that these membrane platforms are derived from the endoplasmic reticulum and are rich in (at least) cholesterol. To extend these studies and identify the cellular lipids critical for WNVKUN replication we utilized a whole cell lipidomics approach and revealed an elevation in phospholipase A2 (PLA2) activity to produce lyso-phosphatidylcholine (lyso-PChol).

Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses.

Although tissue-resident memory T cells (T cells) are critical in fighting infection, their fate after local pathogen re-encounter is unknown. Here we found that skin T cells engaged virus-infected cells, proliferated in situ in response to local antigen encounter and did not migrate out of the epidermis, where they exclusively reside. As a consequence, secondary T cells formed from pre-existing T cells, as well as from precursors recruited from the circulation.

Mapping Organism-wide Immune Responses.

Immune responses are often dissected at the molecular or cellular level, but rarely are they investigated at the scale of the whole organism. Here, Chevrier and colleagues reveal that an interconnected web of protective immunity exists between organs, which safeguards the host from systemic viral spread.

The Host Protein Reticulon 3.1A Is Utilized by Flaviviruses to Facilitate Membrane Remodelling.

Flaviviruses are enveloped, positive-sensed single-stranded RNA viruses that remodel host membranes, incorporating both viral and host factors facilitating viral replication. In this study, we identified a key role for the membrane-bending host protein Reticulon 3.1 (RTN3.

Cutting Edge: Tissue-Resident Memory T Cells Generated by Multiple Immunizations or Localized Deposition Provide Enhanced Immunity.

Tissue-resident memory T cells (T) have been shown to afford superior protection against infection, particularly against pathogens that enter via the epithelial surfaces of the body. Although T are often concentrated at sites of prior infection, it has been shown that T can disseminate throughout the body. We examined the relative effectiveness of global versus targeted CD8 T lodgment in skin.

Transcriptional Enhancers in the Regulation of T Cell Differentiation.

The changes in phenotype and function that characterize the differentiation of naïve T cells to effector and memory states are underscored by large-scale, coordinated, and stable changes in gene expression. In turn, these changes are choreographed by the interplay between transcription factors and epigenetic regulators that act to restructure the genome, ultimately ensuring lineage-appropriate gene expression. Here, we focus on the mechanisms that control T cell differentiation, with a particular focus on the role of regulatory elements encoded within the genome, known as transcriptional enhancers (TEs).

Distinct epigenetic signatures delineate transcriptional programs during virus-specific CD8(+) T cell differentiation.

The molecular mechanisms that regulate the rapid transcriptional changes that occur during cytotoxic T lymphocyte (CTL) proliferation and differentiation in response to infection are poorly understood. We have utilized ChIP-seq to assess histone H3 methylation dynamics within naive, effector, and memory virus-specific T cells isolated directly ex vivo after influenza A virus infection. Our results show that within naive T cells, codeposition of the permissive H3K4me3 and repressive H3K27me3 modifications is a signature of gene loci associated with gene transcription, replication, and cellular differentiation.

T cell immunity as a tool for studying epigenetic regulation of cellular differentiation.

Cellular differentiation is regulated by the strict spatial and temporal control of gene expression. This is achieved, in part, by regulating changes in histone post-translational modifications (PTMs) and DNA methylation that in turn, impact transcriptional activity. Further, histone PTMs and DNA methylation are often propagated faithfully at cell division (termed epigenetic propagation), and thus contribute to maintaining cellular identity in the absence of signals driving differentiation.

Variability of inducible expression across the hematopoietic system of tetracycline transactivator transgenic mice.

The tetracycline (tet)-regulated expression system allows for the inducible overexpression of protein-coding genes, or inducible gene knockdown based on expression of short hairpin RNAs (shRNAs). The system is widely used in mice, however it requires robust expression of a tet transactivator protein (tTA or rtTA) in the cell type of interest. Here we used an in vivo tet-regulated fluorescent reporter approach to characterise inducible gene/shRNA expression across a range of hematopoietic cell types of several commonly used transgenic tet transactivator mouse strains.