Begell House Inc.
Critical Reviews™ in Immunology
CRI
1040-8401
33
3
2013
Glucocorticoid-Induced Apoptosis in Animal Models of Multiple Sclerosis
183-202
10.1615/CritRevImmunol.2013007415
Marco J.
Herold
Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Holger
Reichardt
Institute of Cellular and Molecular Immunology, University of Goettingen Medical School
glucocorticoids
experimental autoimmune encephalomyelitis
apoptosis
neuroinflammation
Glucocorticoids (GCs) are highly potent anti-inflammatory and immunosuppressive agents. They exert influence on many cell types of the immune system and impact a plethora of processes such as cytokine production, leukocyte differentiation, migration and adhesion, apoptosis induction, and changes in morphology.
Those that are most relevant for the modulation of neuroinflammatory diseases, however, are still under
debate. In this review, we will elaborate on how GCs impact inflammatory responses in general and revisit
the ambivalent role that apoptosis plays in animal models of multiple sclerosis. Furthermore, we will discuss
arguments that speak in favor or against an essential function of GC-induced apoptosis in neuroinflammation.
We anticipate that a better knowledge of the mechanisms that GCs employ will eventually find its way into
clinical practice for the future benefit of afflicted patients.
The Yin-Yang of KIR3DL1/S1: Molecular Mechanisms and Cellular Function
203-218
10.1615/CritRevImmunol.2013007409
Geraldine M.
O'Connor
Cancer and Inflammation Program, National Cancer Institute at Frederick, NIH, Frederick
Daniel W.
McVicar
Cancer and Inflammation Program, National Cancer Institute at Frederick, NIH, Frederick
Killer Immunoglobulin-like Receptors
Natural Killer Cells
Human Leukocyte Antigen
Innate Immunity
Killer Immunoglobulin-like Receptors (KIR) are a family of receptors expressed on natural killer (NK) and T-cell subsets. KIR3DL1 is a highly polymorphic receptor that binds to groups of HLAA and HLA-B allotypes that express the Bw4 epitope. The variation in KIR3DL1 allotypes manifests at a number of levels. Most dramatically, a common allelic variant encodes an activating rather than an inhibitory receptor (KIR3DS1). In addition, sequence variants can affect both the frequency of expression within the NK cell population and the intensity of expression on a given cell. KIR3DL1 polymorphism also influences the interaction with HLA-Bw4 molecules, due to contacts with the HLA molecule itself and sensitivity to
the presented peptide. A body of evidence from genetic association studies supports the biological significance
not only of the interaction of KIR3DL1 with HLA-Bw4 but also the functional variation seen with different
KIR3DL1 and HLA allotypes. In this review, we discuss our current understanding of KIR3DL1 function and our recent insights from the structure of the KIR3DL1 in complex with HLA. In addition, we will summarize our current understanding of KIR3DS1, including its ligand specificity and its role in immune responses.
The Role of CARMA1 in T Cells
219-243
10.1615/CritRevImmunol.2013007056
Marly I.
Roche
Pulmonary and Critical Care Unit and the Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
Ravisankar A.
Ramadas
Merck Research Laboratories, Boston, Massachusetts, 02115 USA
Benjamin D.
Medoff
Pulmonary and Critical Care Unit and the Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
CARMA1
T cell
T cell receptor
NF-κB
Caspase recruitment domain-containing membrane-associated guanylate kinase protein-1 (CARMA1), a member of the membrane associated guanylate kinase (MAGUK) family of kinases, is essential for T lymphocyte activation and proliferation via T-cell receptor (TCR) mediated NF-κB activation. Recent studies suggest a broader role for CARMA1 regulating other T-cell functions as well as a role in non-TCR–mediated signaling pathways important for lymphocyte development and functions. In addition,
CARMA1 has been shown to be an important component in the pathogenesis of several human diseases.
Thus, comprehensively defining its mechanisms of action and regulation could reveal novel therapeutic targets
for T-cell–mediated diseases and lymphoproliferative disorders.
Immunotherapeutic Treatment of Autoimmune Diabetes
245-281
10.1615/CritRevImmunol.2013006913
Jae Hyeon
Kim
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine; Kyunggi-do 410-773, Korea
Sang-Man
Jin
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine; Kyunggi-do 410-773, Korea
Hun Sik
Kim
Graduate School, University of Ulsan
Kyoung-Ah
Kim
Department of Medicine, Dongguk University International Hospital, Dongguk University School of Medicine
Myung-Shik
Lee
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine; Kyunggi-do 410-773, Korea
autoimmune diabetes
treatment
prevention
autoantigen
Type 1 diabetes is a prototypic, organ-specific autoimmune disease. Diverse antigen-specific immunotherapy using insulin or glutamic acid decarboxylase peptides and other immunotherapies, such as antibodies, fusion proteins, cytokines, regulatory T cells, small-molecule inhibitors, nonspecific immune modulators, or dietary modifications, have been attempted in human type 1 diabetes. Some of these immunotherapies delay the onset of diabetes or reduce insulin requirements or blood glucose level in patients with established type 1 diabetes. However, most of these immunotherapies failed to induce complete remission of established type 1 diabetes, which could be due to 1) technical difficulties in the achievement of immune tolerance to diabetic autoantigens or in the inhibition of autoimmune responses to those antigens that can be applied to human patients without significant adverse effects, and 2) markedly reduced β-cell mass at the time of disease onset that should be replenished. This review focuses on the immunological aspects of the disease and its treatment, and data from previous or ongoing human clinical trials using immune-logical measures, and recent results from immunological studies employing animal models are discussed.