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The dendritic cell ( DC) lineage is remarkably heterogeneous. It has been postulated that specialized DC subsets have evolved in order to select and support the multitude of possible T cell differentiation pathways. However, defining the function of individual DC subsets has proven remarkably difficult, and DC subset control of key T cell fates such as tolerance, T helper cell commitment and regulatory T cell induction is still not well understood. While the difficulty in assigning unique functions to particular DC subsets may be due to sharing of functions, it may also reflect a lack of appropriate physiological in-vivo models for studying DC function. In this paper we review the limitations associated with many of the current DC models and highlight some of the underlying difficulties involved in studying the function of murine DC subsets. [ABSTRACT FROM AUTHOR]

Summary: Innate lymphoid cells (ILCs) are tissue resident cells that are triggered through a relatively broad spectrum of alarmins, inflammatory cues, neuropeptides, and hormones. Functionally, ILCs are akin to subsets of helper T cells and are characterized by a similar effector cytokine profile. They also share a dependency on many of the same essential transcription factors identified for the maintenance and survival of T cells. The key distinguishing factor between the ILC family and T cells is the lack of antigen-specific T cell receptor (TCR) on ILCs and, thus, they can be considered the "ultimate invariant T cells". ILCs, like T cells, orchestrate downstream effector inflammatory responses by adjusting the cytokine microenvironment in a fashion that promotes protection, health, and homeostasis at mucosal barrier sites. But also, like T cells, ILCs have recently been implicated in several pathological inflammatory disease states. This review focuses on the selective role of ILCs in the development of allergic airway inflammation (AAI) and fibrosis in the gut where a complex ILC interplay has been shown to either attenuate or worsen disease. Finally, we discuss new data on TCR gene rearrangements in subsets of ILCs that challenge the current dogma linking their origin to committed bone marrow progenitors and instead propose a thymic origin for at least some ILCs. In addition, we highlight how naturally occurring TCR rearrangements and the expression of major histocompatibility (MHC) molecules in ILCs provide a useful natural barcode for these cells and may prove instrumental in studying their origins and plasticity. In the lungs, in response to local insult ILC2s initiate a cascade of events that culminate in the expansion and polarization of CD4+ T cells to Th2 cells creating a type 2 immune environment leading to allergic airway inflammation. In the gut, RORα-deficient mice are protected from salmonella-induced intestinal fibrosis due to the failure of RORα-deficient ILC3 to produce functional IL-17. Finally, a new ILC development dogma is proposed where some ILCs undergo non-productive TCR generearrangements in the thymus prior to moving into the periphery and other tissues. [ABSTRACT FROM AUTHOR]

Mandatory maternal metabolic and immunological changes are essential to pregnancy success. Parallel changes in metabolism and immune function make immunometabolism an attractive mechanism to enable dynamic immune adaptation during pregnancy. Immunometabolism is a burgeoning field with the underlying principle being that cellular metabolism underpins immune cell function. With whole body changes to the metabolism of carbohydrates, protein and lipids well recognised to occur in pregnancy and our growing understanding of immunometabolism as a determinant of immunoinflammatory effector responses, it would seem reasonable to expect immune plasticity during pregnancy to be linked to changes in the availability and handling of multiple nutrient energy sources by immune cells. While studies of immunometabolism in pregnancy are only just beginning, the recognised bi-directional interaction between metabolism and immune function in the metabolic disorder obesity might provide some of the earliest insights into the role of immunometabolism in immune plasticity in pregnancy. Characterised by chronic low-grade inflammation including in pregnant women, obesity is associated with numerous adverse outcomes during pregnancy and beyond for both mother and child. Concurrent changes in metabolism and immunoinflammation are consistently described but any causative link is not well established. Here we provide an overview of the metabolic and immunological changes that occur in pregnancy and how these might contribute to healthy versus adverse pregnancy outcomes with special consideration of possible interactions with obesity. Metabolic and immune adaptation are both features of pregnancy. The underlying principle of immunometabolism is that cellular metabolism determines fate and function of immune cells. Immunometabolism might be a key determinant of immune plasticity in pregnancy and modified by obesity for adverse pregnancy outcome. [ABSTRACT FROM AUTHOR]

Summary: Human B cells could be divided into four classical subsets based on CD27 and immunoglobulin (Ig)D expression. Distinct from the other three well‐studied subsets, CD27−IgD− B cells, also termed as double‐negative (DN) B cells, have long been neglected. However, in recent years emerging evidence shows that DN B cells are unique memory B cells with important functions. They are expanded in a variety of diseases, especially in autoimmune diseases, contributing to the disease pathogenesis. Here, we briefly review the studies on DN B cells, including their origins, characteristics, subsets and roles in diseases, to try to bring new insights into this under‐recognized B cell subset. [ABSTRACT FROM AUTHOR]

Summary: Hepatic inflammatory response is a risk factor for liver cancer initiation and progression. Interleukin (IL)‐35 is the newest member of the IL‐12 cytokine family, and has been reported to play an essential role in the immunosuppressive liver microenvironment. Herein we focus on the expression profiles of IL‐35 in hepatocellular carcinoma (HCC) and effects on local immune status. HCC transcriptome array data were downloaded from Gene Expression Omnibus (GEO). Analysis was performed by BRB‐Array Tools and Ingenuity Pathway Analysis (IPA) software. Serum IL‐35 level was detected by AimPlet bead‐based immunoassay. In‐situ IL‐35 detection was performed by immunohistochemical staining and Western blot. The n‐vitro effect of IL‐35 on CD4+ or CD8+ T cell function was detected by flow cytometry. Our results showed that there were large amounts of IL‐35 expressed in HCC serum and tumor tissues. IL‐35 expression affects the transcript of thousands of genes, most differentially expressed genes (DEGs), in tumor tissues correlated with T cell immunity. The IL‐35 high‐expression group exhibited enhancement of regulatory T cells (Tregs) and impairment of cytolytic T cells. In‐vitro experiments proved that exogenous IL‐35 stimulated the expression of programmed cell death 1 (PD‐1) and lymphocyte activation gene‐3 (LAG3) in CD4+ and CD8+ T cells. In addition, the stimulating effect was time‐dependent. Furthermore, IL‐35 inhibited interferon (IFN)‐γ secretion by CD4+ and CD8+ T cells. Elevated IL‐35 had an immune suppressive role in HCC tumor microenvironments through affecting inhibitor receptor expression and cytokine secretion of CD4+ and CD8+ T cells. Dissection of the precise targets and underlying molecular mechanisms would mean alternative treatments for HCC patients. [ABSTRACT FROM AUTHOR]

Summary: Two types of extracellular vesicles (EVs), exosomes and ectosomes, are generated and released by all cells, including immune cells. The two EVs appear different in many properties: size, mechanism and site of assembly, composition of their membranes and luminal cargoes, sites and processes of release. In functional terms, however, these differences are minor. Moreover, their binding to and effects on target cells appear similar, thus the two types are considered distinct only in a few cases, otherwise they are presented together as EVs. The EV physiology of the various immune cells differs as expected from their differential properties. Some properties, however, are common: EV release, taking place already at rest, is greatly increased upon cell stimulation; extracellular navigation occurs adjacent and at distance from the releasing cells; binding to and uptake by target cells are specific. EVs received from other immune or distinct cells govern many functions in target cells. Immune diseases in which EVs play multiple, often opposite (aggression and protection) effects, are numerous; inflammatory diseases; pathologies of various tissues; and brain diseases, such as multiple sclerosis. EVs also have effects on interactive immune and cancer cells. These effects are often distinct, promoting cytotoxicity or proliferation, the latter together with metastasis and angiogenesis. Diagnoses depend on the identification of EV biomarkers; therapies on various mechanisms such as (1) removal of aggression‐inducing EVs; (2) EV manipulations specific for single targets, with insertion of surface peptides or luminal miRNAs; and (3) removal or re‐expression of molecules from target cells. [ABSTRACT FROM AUTHOR]

Since the sequencing of the human genome was completed, attention has turned to examining the functionality of the molecular machinery, in particular of protein expression. Differential proteome analysis by two-dimensional electrophoresis has been adopted to study changes in T cell proteomes during T cell activation, and this work is increasing our understanding of the complexity of signals elicited across multiple pathways. The purpose of this review is to summarize the available evidence in the application of proteomic techniques and methodologies to understand T cell receptor activation from lipid raft and cytoskeletal rearrangements, through to signalling cascades, transcription factor modulation and changes in protein expression patterns. These include post-translational modifications, which are not encoded by the genome. [ABSTRACT FROM AUTHOR]

Fourteen female monkeys (Macaca mulatta) received a trivalent influenza vaccine and antibody response was determined by a change in plasma antibody content (ELISA) before and after vaccine. Lymphocyte cultures were also established from these monkeys and the level of antibody response did not correlate with mitogen-induced lymphocyte blastogenesis or natural killer cell function. In vitro anti-influenza antibody synthesis, however, was found to correlate well with the in vitro response. That is, monkeys who were non-responders, as determined by lack of change in plasma antibody content, were also non-responders in vitro. Accordingly. we believe that vaccine response is not necessarily a measure of immune competence but its measurement may, none the less, have clinical utility. The excellent correlation of in vivo and in vitro response provides predictive value for the in vitro test. Furthermore, because the correlation is good, the in vitro test may be useful as a tool in immunopharmacology and toxicology. [ABSTRACT FROM AUTHOR]

natural killer (NK) cell activity, as measured against K-562 target cells, was evaluated in 23 untreated and in 11 bromocriptine-treated hyperprolactinemia female patients and in 63 age-matched healthy women using 51Cr-release assay. The NK cell activity was significantly reduced in untreated hyperprolactinemia patients with respect to that of normal subjects, but therapy with bromocriptine restored NK cell function of patients to the levels of normal controls. Moreover, a reduced number of Leu-7+ cells and of large granular lymphocytes in hyperprolactinemia patients, as compared to normal controls and bromocriptine-treated subjects, correlated well with the decreased NK activity. Finally, 'in vitro' incubation with purified human prolactin, did not affect NK cell activity of blood mononuclear cells. The present results demonstrate that pathological hyperprolactinemia, in which a tuberoinfundibular dopaminergic defect has been postulated, is also associated with a reduction in NK cell number and function and indicate a possible interaction between prolactin, neuroendocrine system and NK cell lineage in man. [ABSTRACT FROM AUTHOR]

The phenotypic and functional characteristics of the leukaemic cells from one patient with T suppressor ALL were studied at the time of diagnosis and in relapse. At the time of diagnosis, the phenotype corresponded to the intermediate stage between the cortical and medullary phases of normal thymocyte differentiation with a high proportion of T8+ cells (E-R+, TdT+, C3Br-, T3-, T4-, T6+, T8+ +, T10+). Functionally, the cells did not respond to mitogens but mediated strong suppressor activity to allogeneic B-cells, as measured in a reverse haemolytic plaque test. Clinically, the patient exhibited the uncommon feature of hypogammaglobulinaemia. Induction therapy led to complete remission, which continued for 12 months. In the relapse, the phenotype remained essentially stable except for a dramatic decrease of the T8+ cell fraction and an increase of the T10+ cell fraction. Functionally, the suppressor activity was completely lost, indicating a close correlation between phenotype and functional activity in this leukaemic cell population. [ABSTRACT FROM AUTHOR]

The splenic component of mononuclear phagocytic cell function was investigated in rabbits using as a marker the clearance of N-ethylmaleimide-treated. technetium-labelled autologous erythrocytes. In 66 clearances performed in 23 normal rabbits, the clearance N was found to be between 5 and 16 min. the value for each rabbit remaining relatively constant. Clearance was proportional to incubation time or the dose of N-ethylmaleimide used. Clearance was delayed following injection of 20 to 65 mg of preformed complexes of BSA-anti-BSA made in 10-fold antigen excess. The degree and duration of this blockade was related to the dose of the complexes up to a critical value of 20 mg (antibody content) after which no further decrease in clearance occurred although the duration of the blockade was longer at higher doses. Ultracentrifugation studies showed that these complexes were about 14S in size and sequential studies revealed that they were slowly cleared from the circulation. The experiments indicate that studies of splenic function may be of value in assessing immune complex disease, since circulating immune complexes of these characteristics are poorly detected by current methodology. [ABSTRACT FROM AUTHOR]