Begell House Inc.
Critical Reviews™ in Immunology
CRI
1040-8401
34
6
2014
Inhibitory Receptor-Mediated Regulation of Natural Killer Cells
455-465
10.1615/CritRevImmunol.2014012220
Elisenda
Alari-Pahissa
Ludwig Center for Cancer Research, Department of Oncology, University of Lausanne, Epalinges, Switzerland
Camille
Grandclement
Ludwig Center for Cancer Research, Department of Oncology, University of Lausanne, Epalinges, Switzerland
Beena
Jeevan-Raj
Ludwig Center for Cancer Research, Department of Oncology, University of Lausanne, Epalinges, Switzerland
Werner
Held
Ludwig Center for Cancer Research, Department of Oncology, University of Lausanne, Epalinges, Switzerland
inhibitory receptor
ITIM
SHP-1
Vavl
ITSM
SHIP-1
competitive ligand binding
self tolerance
missing-self recognition
Natural killer (NK) cells are capable of directly recognizing pathogens, pathogen-infected cells, and transformed cells. NK cells recognize target cells using approximately 100 germ-line encoded receptors, which display activating or inhibitory function. NK cell activation usually requires the engagement of more than one receptor, and these may contribute distinct signaling inputs that are required for the firm adhesion of NK cells to target cells, polarization, and the release of cytotoxic granules, as well as the production of cytokines. In this article we discuss receptor-mediated mechanisms that counteract NK cell activation. The distinct intracellular inhibitory signaling pathways and how they can dominantly interfere with NK cell activation signaling events are discussed first. In addition, mechanisms by which inhibitory receptors modulate cellular activation at the level of receptor−ligand interactions are described. Receptor-mediated inhibition of NK cell function serves three main purposes: ensuring tolerance of NK cells to normal cells, enabling NK cell responses to aberrant host cells that have lost an inhibitory ligand, and, finally, allowing the recognition of certain pathogens that do not express inhibitory ligands.
Role of LAT1 in the Promotion of Amino Acid Incorporation in Activated T Cells
467-479
10.1615/CritRevImmunol.2014011872
Keitaro
Hayashi
Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan
Naohiko
Anzai
Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan
LAT1
amino acid transporter
T cell
Intake of nutrients from the environment is fundamental to cellular activity. The requirement of nutrients depends on the situation in which cells are placed. Activation of T cells changes the structure and scale of cellular metabolism, which requires a large amount of nutrients. Hydrophilic nutrients such as glucose and amino acids cannot diffuse beyond the cellular membrane; thus transporters are required to assist the incorporation of these nutrients into cells. Based on this observation, metabolic changes accompanying activation of T cells must occur simultaneously with the reorganization of transporters that are capable of providing sufficient nutrients to the cell. This review describes the functional advantages of using special nutrient transporters in activated T cells and discusses the mechanisms of responses to nutrient starvation in T cells.
Plasma Cell Formation, Secretion, and Persistence: The Short and the Long of It
481-499
10.1615/CritRevImmunol.2014012168
Ian
Bayles
Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261
Christine
Milcarek
Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261
immunoglobulin
antibody secreting cells
plasma cells
B-cell differentiation
B cells can be activated by cognate antigen, anti-B-cell receptor antibody, complement receptors, or polyclonal stimulators like lipopolysaccharide; the overall result is a large shift in RNA processing to the secretory-specific form of immunoglobulin (Ig) heavy chain mRNA and an upregulation of Igh mRNA amounts. Associated with this shift is the large-scale induction of Ig protein synthesis and the unfolded protein response to accommodate the massive quantity of secretory Ig that results. Stimulation to secretion also produces major structural accommodations and stress, with extensive generation of endoplasmic reticulum and Golgi as part of the cellular architecture. Reactive oxygen species can lead to either activation or apoptosis based on context and the high or low oxygen tension surrounding the cells. Transcription elongation factor ELL2 plays an important role in the induction of Ig secretory mRNA production, the unfolded protein response, and gene expression during hypoxia. After antigen stimulation, activated B cells from either the marginal zones or follicles can produce short-lived antibody secreting cells; it is not clear whether cells from both locations can become long-lived plasma cells. Autophagy is necessary for plasma cell long-term survival through the elimination of some of the accumulated damage to the ER from producing so much protein. Survival signals from the bone marrow stromal cells also contribute to plasma cell longevity, with BCMA serving a potentially unique survival role. Integrating the various information pathways converging on the plasma cell is crucial to the development of their long-lived, productive immune response.
Role of Human Natural Killer Cells during Epstein-Barr Virus Infection
501-507
10.1615/CritRevImmunol.2014012312
Christian
Muenz
Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
infectious mononucleosis
lytic replication
NKG2D
DNAM-1
NK cell subset
Human natural killer (NK) cells have been suggested to restrict viral infections. However, the evidence for this notion is mostly circumstantial. Recent studies in mice with reconstituted human immune system components, children with symptomatic primary Epstein-Barr virus (EBV) infection, and in secondary lymphoid tissues of healthy EBV carriers have, however, shown that early differentiated human NK cells limit lytic EBV replication and thereby prevent the immunopathological expansion of lytic EBV antigen specific CD8+ T cells that is known as infectious mononucleosis (IM). These findings, which will be discussed in this review, might offer the opportunity to identify EBV negative adolescents at risk to develop IM, and also more generally provide a good example to document restriction of a viral infection by human NK cells.
Role of p53 in Systemic Autoimmune Diseases
509-516
10.1615/CritRevImmunol.2014012193
Hiroaki
Takatori
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan
Hirotoshi
Kawashima
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan
Kotaro
Suzuki
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan
Hiroshi
Nakajima
Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8670, Japan
p53
systemic autoimmune diseases
helper T cell differentiation
The tumor suppressor p53 has been shown to play a central role in tumor suppression by inducing apoptosis, cell cycle arrest, senescence, and DNA repair. In addition, recent observations indicate that the dysfunction of p53 is associated with the development of autoimmune diseases. In this review, we discuss the importance of p53 in various human and murine autoimmune diseases. We also discuss the role of p53 in controlling the balance between Th17 cells and Tregs, the alteration of which is shown to be involved in the development of autoimmunity. It is postulated that the selective restoration of p53 function in T cells could be applicable to the treatment of systemic autoimmune diseases.
Dendritic Cell Cross Talk with Innate and Innate-like Effector Cells in Antitumor Immunity: Implications for DC Vaccination
517-536
10.1615/CritRevImmunol.2014012204
Jasper J. P.
van Beek
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
Florian
Wimmers
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
Stanleyson V.
Hato
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands
I. Jolanda M.
de Vries
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands; Cancer Center Karolinska, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
Annette E.
Skold
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, Netherlands; Cancer Center Karolinska, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
dendritic cells
dendritic cell-based cancer vaccines
natural killer cells
natural killer T cells
γδ T cells
Dendritic cells (DCs) are key players in the induction of immune responses. Adoptive transfer of autologous mature DCs loaded with tumor-associated antigens is a promising therapy for the treatment of immunogenic tumors. For a long time, its therapeutic activity was thought to depend solely on the induction of tumor-specific CD8+ and CD4+ T cell responses. More recently, DCs were shown to bidirectionally interact with innate and innate-like immune cells, including natural killer (NK), invariant natural killer T (iNKT), and γδ T cells. These effector cells can amplify responses induced by DCs via several mechanisms, including induction of DC maturation and conventional T cell priming. In addition, NK, iNKT, and γδ T cells possess cytolytic activity and can act directly on tumor cells. Therapeutic strategies targeting these innate and innate-like immune cells hence hold potential to improve current DC vaccination protocols.
VOLUME 34 CONTENTS, 2014
537-541
10.1615/CritRevImmunol.v34.i6.70