Journal ArticleDOI
Lipid antigen presentation in the immune system: lessons learned from CD1d knockout mice.
Seokmann Hong,David C. Scherer,Nagendra Singh,Sanjeev Kumar Mendiratta,Isao Serizawa,Yasuhiko Koezuka,Luc Van Kaer +6 more
TLDR
Using CD 1d knockout mice, it is demonstrated chat CDI d expression is required for the development of NK T cells, and α‐GalCer can inhibit disease in diabetes‐prone non‐obese diabetic mice, suggesting that α‐ GalCer may be useful for therapeutic intervention in these diseases.Abstract:
CD1 molecules represent a distinct lineage of antigen-presenting molecules that are evolutionarily related to the classical major histocompatibility complex (MHC) class I and class II molecules. Unlike the classical MHC products that bind peptides, CD1 molecules have evolved to bind lipids and glycolipids. Murine and human CD1d molecules can present glycolipid antigens such as alpha-galactosylceramide (alpha-GalCer) to CD1d-restricted natural killer (NK) T cells. Using CD1d knockout mice we demonstrated that CD1d expression is required for the development of NK T cells. These animals were also deficient in the rapid production of interleukin-4 and interferon-gamma in response to stimulation by anti-CD3 antibodies. Despite these defects, CD1d knockout animals were able to generate strong T-helper type 1 (TH1) and TH2 responses. Spleen cells from these animals neither proliferated nor produced cytokines in response to stimulation by alpha-GalCer. Repeated injection of alpha-GalCer into wild-type but not CD1d mutant mice was able to clear metastatic tumors. We further showed that alpha-GalCer can inhibit disease in diabetes-prone non-obese diabetic mice. Collectively, these findings with CD1d knockout animals indicate a critical role for CD1d-dependent T cells in various disease conditions, and suggest that alpha-GalCer may be useful for therapeutic intervention in these diseases.read more
Citations
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Journal ArticleDOI
NKT cells: facts, functions and fallacies
TL;DR: This review aims to provide an update on NKT cell biology and, whenever possible, to compare what is known about NKT-cell subsets.
Journal ArticleDOI
Going both ways: Immune regulation via CD1d-dependent NKT cells
TL;DR: This review will explore the diverse influences of NKT cells in various disease models, their ability to suppress or enhance immunity, and the potential for manipulating these cells as a novel form of immunotherapy.
Journal ArticleDOI
The interactions between inflammation and coagulation
TL;DR: Downregulation of anticoagulant pathways not only promotes thrombosis but also amplifies the inflammatory process, such as manifested in severe sepsis or inflammatory bowel disease.
Journal ArticleDOI
The Protein C Pathway
TL;DR: Animal studies and preliminary clinical results suggest that protein C/activated protein C supplementation may be useful in reversing microvascular dysfunction, and the mechanisms by which inflammation impairs the function of this pathway are reviewed.
Journal ArticleDOI
Natural Killer T Cell Activation Inhibits Hepatitis B Virus Replication in Vivo
TL;DR: It is concluded that α-GalCer inhibits HBV replication by directly activating NKT cells and by secondarily activating NK cells to secrete antiviral cytokines in the liver, and that therapeutic activation of N KT cells may represent a new strategy for the treatment of chronic HBV infection.
References
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Functional diversity of helper T lymphocytes.
TL;DR: The existence of subsets of CD4+ helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses.
Journal ArticleDOI
CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides.
Tetsu Kawano,Junqing Cui,Yasuhiko Koezuka,Isao Toura,Yoshikatsu Kaneko,Kazuhiro Motoki,Hitomi Ueno,Ryusuke Nakagawa,Hiroshi Sato,Eisuke Kondo,Haruhiko Koseki,Masaru Taniguchi +11 more
TL;DR: Glycosylceramide-mediated proliferative responses of Valpha14 NKT cells were abrogated by treatment with chloroquine-concanamycin A or by monoclonal antibodies against CD1d/Vbeta8, CD40/CD40L, or B7/CTLA-4/CD28, but not by interference with the function of a transporter-associated protein.
Journal ArticleDOI
Nk cell receptors
TL;DR: Three distinct receptor families, Ly49, CD94/NKG2, and KIR, are involved in NK cell recognition of polymorphic MHC class I molecules and a common pathway of inhibitory signaling is provided by ITIM sequences in the cytoplasmic domains of these otherwise structurally diverse receptors.
Journal ArticleDOI
MOUSE CD1-SPECIFIC NK1 T CELLS: Development, Specificity, and Function
TL;DR: The specificity and function of mouse NK1 T cells are reviewed, the relationship of this lineage to mainstream T cells and NK cells is discussed, and the novel regulatory pathway, which straddles the innate and the adaptive immune systems, is discussed.
Journal ArticleDOI
Requirement for Vα14 NKT Cells in IL-12-Mediated Rejection of Tumors
Junqing Cui,Tahiro Shin,Tetsu Kawano,Hiroshi Sato,Eisuke Kondo,Isao Toura,Yoshikatsu Kaneko,Haruhiko Koseki,Masamoto Kanno,Masaru Taniguchi +9 more
TL;DR: The Vα14 NKT cell–deficient mice could no longer mediate the interleukin-12 (IL-12)–induced rejection of tumors, and they mediated their cytotoxicity by an NK-like effector mechanism after activation with IL-12.