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E and inhibitor of DNA binding (ID) proteins are transcriptional regulators that function in many developmental processes in vertebrates and invertebrates. One subset of E proteins, the E2A proteins, have a central role in the transcriptional regulatory networks that promote commitment to and differentiation of the B- and T-cell lineages, and their function in these lineages is modulated by ID proteins. In this Review, I discuss recent studies that reveal a more extensive role for E and ID proteins in the transcriptional networks that drive the differentiation of many lymphoid lineages, as well as new functions for these proteins in haematopoietic stem cells and their multipotent, but lymphoid-primed, progeny. [ABSTRACT FROM AUTHOR]

Presents an update on papers related to immunology as of January 2003. Role of a peptide in the activation of natural killer cells; Discovery of the non-T-cell activation linker; Adaptor involved in Toll-like receptor signaling.

The article presents research from the field of tumour immunology based on the original research paper "Vα24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages," by L. Song et al. that appeared in the May 1, 2009 issue of the "Journal of Clinical Investigation." Cancer models, macrophages, monocytes, invariant natural killer T (iNKT) cells, and glycolipids are mentioned.

The article reports that a ligand for the human natural killer (NK) cell activating receptor NKp80, called the activation-induced C-type lectin (AICL), has been identified. The interaction between NKp80 and AICL results in the mutual activation of both the NK cell and the myeloid cell. The ligation of NKp80 with a specific antibody stimulates NK-cell cytotoxicity and cytokine release, which shows that it is consistent with being an activating receptor.

An abstract of the article "The transcription factor Zbtb32 controls the proliferative burst of virus-specific natural killer cells responding to infection" by A. M. Beaulieu and colleagues is presented.

The article presents information on a research study conducted by researchers S. Xiong and colleagues, published in the "Journal of Clinical Investigation," which shows that maternal uterine natural killer (NK) cell-activating receptor KIR2DS1 enhances placentation.

The article offers information on the results of a new study which demonstrate the modulation of the natural killer (NK) cell activity by the endogenous and exogenous ligands for the aryl hydrocarbon receptor (AHR).

The article offers information on a study that sheds light on the heterogeity of invariant natural killer (iNKT) cells by defining the functional and the developmental properties of distinct subsets in mice.

The article presents abstracts of papers on immunology including "Ozone exposure in a mouse model induces airway hyperactivity that requires the presence of natural killer T cells and IL-17," by M. Pichavant and colleagues, and "Repression of the transcription factor Th-POX by Runx complexes in cytotoxic T cell development," by R. Setoguchi and colleagues.

Discusses two research focusing on how natural killer T (NKT) cells detect microorganisms. Recognition of bacterial glycosphingolipids by NKT cells; Antigens that activate NKT cells during microbial infections.

The article focuses on a study that investigates the function and maturation of natural killer (NK) cells. It notes that the development of NK cells are affected on the absence of the T-box transcription factors T-bet and eomesodermin as exemplified on the condition of a mice that was used in the study. It has further concluded that NK cell responsiveness may be therapeutically boosted by prohibiting NKp46.

Discusses research being done on CD1d-restricted natural killer T (NKT) cells. Reference to a study by O. Akbari et al published in a 2006 issue of "The New England Journal of Medicine"; Role of NKT cells in the development of allergen-induced airway hyperractivity in allergic asthma; Methods used to examine the role of NKT cells in asthma.

Discusses research by Cornelia Urlich and colleagues published in the "Journal of the American Dietetic Association" on the impact of yo-yo dieting on the immune function. Examination of interview responses from women who underwent weight loss diets; Implications of weight cycling for natural killer cell function; Recommended solutions to the negative effects of weight loss on the immune system.

The article cites two studies which found that interleukin-22 (IL-22)-producing T helper cells has been added to the increasing diversity of cluster of differentiation 4 (CD4)[+] T[H] cell subsets. They showed that it produced by T[H]17 and by some natural killer cell-like subsets. They revealed that it was less dependent on the expression of the transcription factor retinoic acid receptor-related -yt compared with IL-17 production.

Host restriction factors are potent, widely expressed intracellular blocks to viral replication that are an important component of the innate immune response to viral infection. However, viruses have evolved mechanisms that antagonize restriction factors. Through evolutionary pressure for both host survival and virus replication, an evolutionary 'arms race' has developed that drives continuous rounds of selection for beneficial mutations in the genes encoding restriction factors and their viral antagonists. Because viruses can evolve faster than their hosts, the innate immune system of modern-day vertebrates is for the most part optimized to defend against ancient viruses, rather than newer viral threats. Thus, the evolutionary history of restriction factors might, in part, explain why humans are susceptible or resistant to the viruses present in the modern world. [ABSTRACT FROM AUTHOR]

The article presents abstracts on medical topics which include the natural killer cells relative to dendritic cells and murine's development and function, and another about t-cell responses with mice suppress airway inflammation, airway-hyperreactivity, and fibrosis.

The article reports that glycosphingolipid isoglobotrihexosylceramide (iGb3) is not the ligand involved in the positive choice of invariant natural killer T (iNKT) cells in the thymus. Studies reveal decreased magnitudes of iNKT cells in some mouse models of glycosphingolipid storage diseases which do not interfere primarily in iGb3 formation. Results likewise do not support iGb3 participation in the positive selection of iNKT cells in mouse or human thymus.

The article presents brief on Immunology research. A research on the role of mitochondria in lymphocyte chemotaxis is presented. An overview on the iteractions between NK cells and accessory cells to determine immune response to P. falciparum is presented. The physiological functions of CD28 in t-cells is discussed.

The potent lipid mediator sphingosine-1-phosphate (S1P) is produced inside cells by two closely related kinases, sphingosine kinase 1 (SPHK1) and SPHK2, and has emerged as a crucial regulator of immunity. Many of the actions of S1P in innate and adaptive immunity are mediated by its binding to five G protein-coupled receptors, designated S1PR1-5, but recent findings have also identified important roles for S1P as a second messenger during inflammation. In this Review, we discuss recent advances in our understanding of the roles of S1P receptors and describe the newly identified intracellular targets of S1P that are crucial for immune responses. Finally, we discuss the therapeutic potential of new drugs that target S1P signalling and functions. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) and natural killer (NK) cells have central roles in antiviral immunity by shaping the quality of the adaptive immune response to viruses and by mediating direct antiviral activity. HIV-1 infection is characterized by a severe dysregulation of the antiviral immune response that starts during early infection. This Review describes recent insights into how HIV-1 infection affects DC and NK cell function, and the roles of these innate immune cells in HIV-1 pathogenesis. The importance of understanding DC and NK cell crosstalk during HIV infection for the development of effective antiviral strategies is also discussed. [ABSTRACT FROM AUTHOR]

Natural killer T (NKT) cells are important regulatory lymphocytes that have been shown in mouse studies, to have a crucial role in promoting immunity to tumours, bacteria and viruses, and in suppressing cell-mediated autoimmunity. Many clinical studies have indicated that NKT cell deficiencies and functional defects might also contribute to similar human diseases, although there is no real consensus about the nature of the NKT cell defects or whether NKT cells could be important for the diagnosis and/or treatment of these conditions. In this Review, we describe the approaches that have been used to analyse the NKT cell populations of various patient groups, suggest new strategies to determine how (or indeed, if) NKT cell defects contribute to human disease, and discuss the prospects for using NKT cells for therapeutic benefit. [ABSTRACT FROM AUTHOR]

Discusses research being done on a combination therapy for the treatment of cancer. Reference to a study by S. H. Thorne et al published in a 2006 issue of "Science"; Information on the two antitumour approaches combined by the researchers to achieve specific targeting of tumours; Efficacy of the combination therapy.

Gammadelta T cells have several innate cell-like features that allow their early activation following recognition of conserved stress-induced ligands. Here we review recent observations revealing the ability of gammadelta T cells to rapidly produce cytokines that regulate pathogen clearance, inflammation and tissue homeostasis in response to tissue stress. These studies provide insights into how they acquire these properties, through both developmental programming in the thymus and functional polarization in the periphery. Innate features of gammadelta T cells underlie their non-redundant role in several physiopathological contexts and are therefore being exploited in the design of new immunotherapeutic approaches. [ABSTRACT FROM AUTHOR]

The development of type 1 diabetes involves a complex interaction between pancreatic beta-cells and cells of both the innate and adaptive immune systems. Analyses of the interactions between natural killer (NK) cells, NKT cells, different dendritic cell populations and T cells have highlighted how these different cell populations can influence the onset of autoimmunity. There is evidence that infection can have either a potentiating or inhibitory role in the development of type 1 diabetes. Interactions between pathogens and cells of the innate immune system, and how this can influence whether T cell activation or tolerance occurs, have been under close scrutiny in recent years. This Review focuses on the nature of this crosstalk between the innate and the adaptive immune responses and how pathogens influence the process. [ABSTRACT FROM AUTHOR]

Inflammation is a multicomponent response to tissue stress, injury and infection, and a crucial point of its control is at the level of gene transcription. The inducible inflammatory gene expression programme--such as that triggered by Toll-like receptor signalling in macrophages--is comprised of several coordinately regulated sets of genes that encode key functional programmes; these are controlled by three classes of transcription factors, as well as various transcriptional co-regulators and chromatin modifications. Here, we discuss the mechanisms of and the emerging principles in the transcriptional regulation of inflammatory responses in diverse physiological settings. [ABSTRACT FROM AUTHOR]

Mucosal tissues, lying at the interface with the external environment, are constantly challenged by microbial, physical and chemical assaults. To provide the necessary immune defence to such challenges, lymph nodes and Peyer's patches are formed in utero in response to inductive signals from lymphoid-tissue inducer (LTi) cells. As discussed in this Progress article, a series of recent reports has identified a population of interleukin-22-producing mucosal cells in the gut and tonsils that share features with both LTi cells (by expressing RORgammat) and natural killer cells (by expressing NKp46) and that might be involved in immunity and homeostasis in mucosal tissues. [ABSTRACT FROM AUTHOR]

Mutations that affect the adaptor molecule SLAM-associated protein (SAP) underlie the primary immunodeficiency disease X-linked lymphoproliferative syndrome. SAP is required for mediating signals from members of the signalling lymphocytic activation molecule (SLAM) family of immunomodulatory receptors. Recent data have highlighted a role for SAP in the development of innate-like T-cell lineages, including natural killer T cells, and in the regulation of the interactions between B cells and T cells that are required for germinal-centre formation and long-term humoral immunity. These data have revealed that SLAM family members and SAP have crucial roles in regulating lymphocyte interactions and adhesion, which are required for the normal development, homeostasis and function of the immune system. [ABSTRACT FROM AUTHOR]

Discusses research being done on the association of the combination of maternal killer-cell immunoglobulin-like receptor (KIR) and fetal HLA-C genotypes with increased risk of pre-eclampsia. Reference to a study by S. E. Hiby et al published in a 2004 issue of the "Journal of Experimental Medicine"; Information on pre-eclampsia; Role of maternal natural killer cells; Analysis of the frequency of maternal KIR and fetal HLA-C genotypes in pregnant women with pre-eclampsia and those with normal pregnancies.

Discusses research being done on KIR2DL3, an inhibitory natural killer-cell receptor. Reference to a study by S.I. Khakoo et al published in the 2004 issue of "Science"; Human leucocyte antigen-C1 (HLA-C1) homozygosity; Association of the KIR2DL3;HLA-C1 homozygous genotype with resolution of hepatitis C virus infection.

Deals with the findings of a report on the method in which maternal immune system tolerate the persistence of paternal alloantigens during pregnancy. Factors which contributed to fetal evasion from immune attack; Result of the activation of natural killer cells; Expansion of maternal regulatory T-cell populations.

Discusses research being done on the involvement of a natural killer (NK) cell receptor in eliciting allograft rejection. Reference to a study by J. Kolke and colleagues published in a 2004 issue of "Journal of Experimental Medicine"; Characteristics of the NK cell receptor; Expression of the NK cell receptor.

The natural killer (NK)-cell immunological synapse is the dynamic interface formed between an NK cell and its target cell. Formation of the NK-cell immunological synapse involves several distinct stages, from the initiation of contact with a target cell to the directed delivery of lytic-granule contents for target-cell lysis. Progression through the individual stages is regulated, and this tight regulation underlies the precision with which NK cells select and kill susceptible target cells (including virally infected cells and cancerous cells) that they encounter during their routine surveillance of the body. [ABSTRACT FROM AUTHOR]

The conventional wisdom is that cell-surface receptors interact with ligands expressed on other cells to mediate cell-to-cell communication (trans interactions). Unexpectedly, it has recently been found that two classes of receptors specific for MHC class I molecules not only interact with MHC class I molecules expressed on opposing cells, but also with those on the same cell. These cis interactions are a feature of immunoreceptors that inhibit, rather than activate, cellular functions. Here, we review situations in which cis interactions have been observed, the characteristics of receptors that bind in trans and cis, and the biological roles of cis recognition. [ABSTRACT FROM AUTHOR]

Discusses research being done on the identification of a perfect match for the natural killer-cell receptor DNAX accessory molecule 1 (DNAM1). Reference to a study by C. Bottino et al., published in the 2003 issue of the "Journal of Experimental Medicine"; Identification of cell surface ligands for the human DNAM-1 activating molecule.

Offers information on the mechanics of signaling pathways selection in natural killer (NK) cells. Activation of NK cells; Influence of immunoreceptor tyrosine-based activation motif on NK cell cytotoxicity; Physiological transport of NK cells.

Natural killer (NK) cells are large granular lymphocytes capable of producing inflammatory cytokines and spontaneously killing malignant, infected or 'stressed' cells. These NK-cell functions are controlled by cell-surface receptors that titrate stimulatory and inhibitory signals. However, we remain puzzled about where and when NK cells develop and differentiate, and this has fuelled the debate over the diversification of the peripheral NK-cell pool: are NK cells functionally homogeneous or are there subsets with specialized effector functions? In this Review, we consider the developmental relationships and biological significance of the diverse NK-cell subsets in mice and humans, and discuss how new humanized mouse models may help to characterize them further. [ABSTRACT FROM AUTHOR]

CD1d-dependent natural killer T (NKT) cells are a unique T-cell subset with the ability to regulate the immune system in response to a broad range of diseases. That low NKT-cell numbers are associated with many different disease states in mice and humans, combined with the fact that NKT-cell numbers vary widely between individuals, makes it crucial to understand how these cells develop and how their numbers are maintained. Here, we review the current state of knowledge of NKT-cell development and attempt to highlight the most important questions in this field. [ABSTRACT FROM AUTHOR]

Current insights into the molecular specificities that regulate natural killer (NK)-cell function suggest that it might be possible to design NK-cell-based immunotherapeutic strategies against human cancer. Here, we describe evidence for NK-cell targeting of human tumours and address crucial questions that, in our opinion, require consideration for the development of successful NK-cell-based therapies. Appropriately used, we predict that NK cells will have a role, both directly and in combination with other treatment modalities, in future treatment of cancer. [ABSTRACT FROM AUTHOR]

Presents the results of a study which discussed the pathophysiologic mechanisms of natural killer cells. Regulation of perforin gene expression; Results of bone-marrow transfer experiments; Observation on symptoms similar to that of familial haemophagocytic lymphohistiocytosis.

Discusses research which revealed a third-type dendritic cell (DC)-lymphocyte collaboration. Information on human dendritic cell (DC)-natural killer (NK) cell interactions; Enhancement of NK-cell activation by DC; Importance of the DC-NK ratio in determining the outcome of the interaction; Basis of DC-NK interaction.

Focuses on the mechanisms employed by hepatitis C virus (HCV) to promote chronic infection. Result of crosslinking CD81 with HCV envelope protein E2; Function of CD81; Inhibition of the Interferon-γ production in response to NK-cell stimulation by the cytokines interleukins.

Presents updates on immunology research as of February 2002. Non-participation of interleukin-9 in either the development of allergen-induced pulmonary inflammation nor airway hyper-reactivity; Homeostatic competition between T cells revealed by conditional inactivation of the mouse Cd4 gene; Identification of the earliest prethymic bipotent T/NK progenitor in murine fetal liver.

The initiation and the progression of autoimmune diseases stem from complex interactions that involve cells of both the innate and the adaptive immune system. As we discuss here, natural killer (NK) cells, which are components of the innate immune system, can inhibit or promote the activation of autoreactive T cells during the initiation of autoimmunity. After they have been activated, autoreactive T cells contribute to the homeostatic contraction of NK-cell populations. The dynamic interaction between NK cells and autoreactive T cells might indicate the transition from the innate immune triggering of autoimmunity to the progressive phase of the disease. Understanding the mechanisms and signals that control the reciprocal regulation of NK cells and autoreactive T cells could have important implications for treatment in the clinic. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells, similar to other lymphocytes, acquire tolerance to self. This means that NK cells have the potential to attack normal self cells but that there are mechanisms to ensure that this does not usually occur. Self-tolerance is acquired by NK cells during their development, but the underlying molecular and cellular mechanisms remain poorly understood. Recent studies have produced important new information about NK-cell self-tolerance. Here, we review the evidence for and against possible mechanisms of NK-cell self-tolerance, with an emphasis on the role of MHC-specific receptors. [ABSTRACT FROM AUTHOR]

Reports on the results of studies on the effect of natural killer (NK) cells on tumor cells. Role of NK cells in rejecting tumor cells; Implications for tumor vaccine development.

A fundamental tenet of the immune system is the requirement for lymphocytes to respond to transformed or infected cells while remaining tolerant of normal cells. Natural killer (NK) cells discriminate between self and non-self by monitoring the expression of MHC class I molecules. According to the 'missing-self' hypothesis, cells that express self-MHC class I molecules are protected from NK cells, but those that lack this self-marker are eliminated by NK cells. Recent work has revealed that there is another system of NK-cell inhibition, which is independent of MHC class I molecules. Newly discovered NK-cell inhibitory receptors that have non-MHC-molecule ligands broaden the definition of self as seen by NK cells. [ABSTRACT FROM AUTHOR]

Immune responses are generally divided into innate and adaptive responses, and the efficacy of one is thought to be independent of the other. The regulation of immune responses, however, is complex, and accumulating evidence indicates that multiple interactions between immune effector cells are common and are crucial for the initiation, as well as the outcome, of these responses. Dendritic cells, long recognized as key initiators of primary adaptive immunity, are now also seen as crucial regulators of aspects of innate immunity, in particular natural-killer-cell function. Reciprocally, natural killer cells can influence the activity of dendritic cells. Here, we review recent exciting progress in this field, and we highlight the impact of this cellular crosstalk on the design of immune-based therapies for control of infection and cancer. [ABSTRACT FROM AUTHOR]

Autoimmune responses are normally kept in check by immune-tolerance mechanisms, which include regulatory T cells. In recent years, research has focused on the role of a subset of natural killer T (NKT) cells-invariant NKT (iNKT) cells, which are a population of glycolipid-reactive regulatory T cells-in controlling autoimmune responses. Because iNKT cells strongly react with a marine-sponge-derived glycolipid,a-galactosylceramide (a-GalCer), it has been possible to specifically target and track these cells. As I discuss here, although preclinical studies have shown considerable promise for the development of treatment witha-GalCer as a therapeutic modality for autoimmune diseases, several obstacles need to be overcome before movinga-GalCer therapy from the bench to the bedside. [ABSTRACT FROM AUTHOR]

Transcription factors have a profound influence on both the differentiation and effector function of cells of the immune system. T-bet controls the cytotoxicity of CD8(+) T cells and the production of interferon-gamma, and it also affects the development and function of natural killer cells and natural killer T cells. Other factors such as eomesodermin, MEF, ETS1 and members of the interferon-regulatory factor family also contribute to the effector function of immune cells. In this review, we focus on recent studies that have shed light on the transcriptional mechanisms that regulate cellular effector function in the immune system. [ABSTRACT FROM AUTHOR]

Recent years have seen so-called natural killer T (NKT) cells emerge as important regulators of the immune response. The existence of NKT-cell subsets, and other types of T cell that resemble NKT cells, is an ongoing source of confusion in the literature. This perspective article seeks to clarify which cells fall under the NKT-cell umbrella, and which might be best considered as separate. [ABSTRACT FROM AUTHOR]