A narrow T cell receptor repertoire instructs thymic differentiation of MHC class Ib-restricted CD8+ regulatory T cells.

Although most CD8+ T cells are equipped to kill infected or transformed cells, a subset may regulate immune responses and preserve self-tolerance. Here, we describe a CD8 lineage that is instructed to differentiate into CD8 T regulatory cells (Tregs) by a surprisingly restricted set of T cell receptors (TCRs) that recognize MHC-E (mouse Qa-1) and several dominant self-peptides. Recognition and elimination of pathogenic target cells that express these Qa-1-self-peptide complexes selectively inhibits pathogenic antibody responses without generalized immune suppression.

Parainfluenza and corona viruses in a fallow deer () with fatal respiratory disease.

Parainfluenza virus type 3 (PIV-3) and coronaviruses (CoV) are commonly found in respiratory tracts of ruminants and capable of causing clinical disease. Here, we investigated the cause of ill-thrift and sudden death in a five-month-old male fallow deer which occurred in December 2019. The calf was one of the five calves in a herd of 170 deer that, along with three adult hinds, died during a 2-week period.

Reindeer health and welfare.

This focus article has been prepared by Aiden Foster of the University of Bristol (which offers postmortem examination services as part of the APHA surveillance network) and Alan Wight, veterinary lead of the APHA Miscellaneous and Exotic Farmed Species Expert Group.

Antibody-mediated blockade of the IL23 receptor destabilizes intratumoral regulatory T cells and enhances immunotherapy.

Regulatory T cells (Treg) can impede antitumor immunity and currently represent a major obstacle to effective cancer immunotherapy. Targeting tumor-infiltrating regulatory Treg while sparing systemic Treg represents an optimal approach to this problem. Here, we provide evidence that the interleukin 23 receptor (IL23R) expressed by tumor-infiltrating Treg promotes suppressive activity.

Quiescent cancer cells resist T cell attack by forming an immunosuppressive niche.

Immunotherapy is a promising treatment for triple-negative breast cancer (TNBC), but patients relapse, highlighting the need to understand the mechanisms of resistance. We discovered that in primary breast cancer, tumor cells that resist T cell attack are quiescent. Quiescent cancer cells (QCCs) form clusters with reduced immune infiltration.

Definition of a mouse microglial subset that regulates neuronal development and proinflammatory responses in the brain.

Expression of (encoding the CD11c surface protein) and (encoding osteopontin; OPN) has been associated with activated microglia that can develop in healthy brains and some neuroinflammatory disorders. However, whether CD11c and OPN expression is a consequence of microglial activation or represents a portion of the genetic program expressed by a stable microglial subset is unknown. Here, we show that OPN production in the brain is confined to a small CD11c microglial subset that differentiates from CD11c precursors in perinatal life after uptake of apoptotic neurons.

Review of investigations of premises housing animals that were linked to human outbreaks of cryptosporidiosis in England and Wales between 2009 and 2019.

Background: Cryptosporidium can be an important human health risk, predominantly causing gastroenteritis. With increased public attendance at commercial and open farms, there is a need to improve the understanding of Cryptosporidium risk on premises that are visited by the public.

Methods: This study was designed to explore the animal premises-related and animal sampling-related data routinely collected, during 2009-2019, from human outbreak sampling investigations where animal contact was suggested as a source of Cryptosporidium.

A Central Role for Ly49 Receptors in NK Cell Memory.

In the past decade, the study of NK cells was transformed by the discovery of three ways these "innate" immune cells display adaptive immune behavior, including the ability to form long-lasting, Ag-specific memories of a wide variety of immunogens. In this review, we examine these types of NK cell memory, highlighting their unique features and underlying similarities. We explore those similarities in depth, focusing on the role that Ly49 receptors play in various types of NK cell memory.

Small-scale pig producers and disease surveillance: key threats.

A series of meetings for small-scale pig producers raised awareness of surveillance for pig diseases in Great Britain and highlighted different types of disease threat. This focus article summarises some key messages from those meetings and two of the threats discussed.

Programmed death ligand 1 expression in EBUS aspirates of non-small cell lung cancer: Is interpretation affected by type of fixation?

Background: Much of the reluctance about using cytology specimens rather than histology specimens to assess programmed death ligand 1 (PD-L1) expression for guiding the use of immune modulating drugs in the management of non-small cell lung cancer (NSCLC) is based on the belief that the alcohol-based fixatives favored by cytopathologists might reduce the antigenicity of PD-L1 and lead to artifactually low expression levels and false-negative reporting. Therefore, this study was performed to determine whether there is any difference in PD-L1 expression between endobronchial ultrasound (EBUS)-guided aspirates of NSCLC fixed in alcohol-based fixatives and those fixed in neutral buffered formalin (NBF), the standard laboratory fixative for histology specimens.

Methods: The expression of PD-L1 was compared in 50 paired EBUS aspirates of NSCLC taken from the same lymph node during the same procedure.

Critical role for the Ly49 family of class I MHC receptors in adaptive natural killer cell responses.

Adaptive natural killer (NK) cell memory represents a new frontier in immunology. Work over the last decade has discovered and confirmed the existence of NK cells with antigen-specific memories, which had previously been considered a unique property of T and B cells. These findings have shown that antigen-specific NK cells gain their specificity without the use of RAG proteins, representing a novel mechanism for generating antigen specificity, but the details of this mechanism have remained a mystery.

Differentiated macrophages acquire a pro-inflammatory and cell death-resistant phenotype due to increasing XIAP and p38-mediated inhibition of RipK1.

Monocytes differentiate into macrophages, which deactivate invading pathogens. Macrophages can be resistant to cell death mechanisms in some situations, and the mechanisms involved are not clear. Here, using mouse immune cells, we investigated whether the differentiation of macrophages affects their susceptibility to cell death by the ripoptosome/necrosome pathways.

Directional preference of activation of abdominal and paraspinal muscles during position-control tasks in sitting.

Controversy exists in the literature regarding antagonist activity of trunk muscles during different types of trunk loading, and the direction-specificity of activation of trunk muscles, particularly the deeper trunk muscles. This study aimed to systematically compare activation of a range of trunk muscles between directions of statically applied loads, and to consider the impact of breathing in this activation. In a semi-seated position, 13 healthy male participants resisted moderate inertial loads applied to the trunk in eight different directions.

Expansion and Protection by a Virus-Specific NK Cell Subset Lacking Expression of the Inhibitory NKR-P1B Receptor during Murine Cytomegalovirus Infection.

NK cells play a major role in immune defense against human and murine CMV (MCMV) infection. Although the MCMV genome encodes for MHC class I-homologous decoy ligands for inhibitory NK cell receptors to evade detection, some mouse strains have evolved activating receptors, such as Ly49H, to recognize these ligands and initiate an immune response. In this study, we demonstrate that approximately half of the Ly49H-expressing (Ly49H(+)) NK cells in the spleen and liver of C57BL/6 mice also express the inhibitory NKR-P1B receptor.

Nucleosome Presence at AML-1 Binding Sites Inversely Correlates with Ly49 Expression: Revelations from an Informatics Analysis of Nucleosomes and Immune Cell Transcription Factors.

Beyond its role in genomic organization and compaction, the nucleosome is believed to participate in the regulation of gene transcription. Here, we report a computational method to evaluate the nucleosome sensitivity for a transcription factor over a given stretch of the genome. Sensitive factors are predicted to be those with binding sites preferentially contained within nucleosome boundaries and lacking 10 bp periodicity.

Influenza Virus Targets Class I MHC-Educated NK Cells for Immunoevasion.

The immune response to influenza virus infection comprises both innate and adaptive defenses. NK cells play an early role in the destruction of tumors and virally-infected cells. NK cells express a variety of inhibitory receptors, including those of the Ly49 family, which are functional homologs of human killer-cell immunoglobulin-like receptors (KIR).