CD4+ Type II NKT Cells Mediate ICOS and Programmed Death-1–Dependent Regulation of Type 1 Diabetes

Kadri, Nadir; Korpos, Éva; Gupta, Shashank; Briet, Claire; Löfbom, Linda; Yagita, Hideo; Lehuen, Agnès; Boîtard, Christian; Holmberg, Dan; Sorokin, Lydia; Cardell, Susanna

doi:10.4049/jimmunol.1101390

Cited by 48 publications

(44 citation statements)

References 54 publications

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“…Consistent with the role of tolerized DCs, our data clearly show that adoptive transfer of DCs alone from sulfatide-treated animals is able to protect recipients from EAE. We are investigating potential pathways including ERK1/2 signaling (49) or IL-10 secretion (50) or ICOS/PD-1 dependent signaling (51, 52) by which DCs are tolerized following NKT cell subset interactions leading to control of inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cells and Anergic Type I NKT Cells Play a Crucial Role in Sulfatide-Mediated Immune Regulation in Experimental Autoimmune Encephalomyelitis

Maricic

Halder

Bischof

et al. 2014

The Journal of Immunology

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CD1d-restricted NKT cells can be divided into two groups: type I NKT cells utilize a semi-invariant TCR whereas type II express a relatively diverse set of TCRs. A major subset of type II NKT cells recognizes myelin-derived sulfatides and is selectively enriched in the central nervous system tissue during experimental autoimmune encephalomyelitis (EAE). We have shown that activation of sulfatide-reactive type II NKT cells by sulfatide prevents induction of EAE. Here we have addressed the mechanism of regulation as well as whether a single immunodominant form of synthetic sulfatide can treat ongoing chronic and relapsing EAE in SJL/J mice. We have shown that the activation of sulfatide-reactive type II NKT cells leads to a significant reduction in the frequency and effector function of PLP139-151/I-As–tetramer+ cells in lymphoid and CNS tissues. In addition, type I NKT cells and dendritic cells in the periphery as well as CNS-resident microglia are inactivated following sulfatide administration, and mice deficient in type I NKT cells are not protected from disease. Moreover tolerized DCs from sulfatide-treated animals can adoptively transfer protection into naive mice. Treatment of SJL/J mice with a synthetic cis-tetracosenoyl sulfatide, but not αGalCer, reverses ongoing chronic and relapsing EAE. Our data highlight a novel immune regulatory pathway involving NKT subset interactions leading to inactivation of type I NKT cells, DCs, and microglial cells in suppression of autoimmunity. Since CD1 molecules are non-polymorphic, the sulfatide-mediated immune regulatory pathway can be targeted for development of non-HLA-dependent therapeutic approaches to T cell-mediated autoimmune diseases.

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Section: Discussionmentioning

confidence: 99%

Dendritic Cells and Anergic Type I NKT Cells Play a Crucial Role in Sulfatide-Mediated Immune Regulation in Experimental Autoimmune Encephalomyelitis

Maricic

Halder

Bischof

et al. 2014

The Journal of Immunology

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“…We have shown that type II NKT cells from 24αβ transgenic mice can protect NOD mice from disease, dependent on costimulators inducible costimulator (ICOS) and PD1 interactions (45, 46). Besides being a major lipid in the myelin sheath, different species of sulfatide are also present in pancreatic β-cells and could serve as ligands for type II NKT cells during T1D immunopathogenesis (47).…”

Section: Type II Nkt Cells In Different Diseasesmentioning

confidence: 99%

Type II NKT Cells: An Elusive Population With Immunoregulatory Properties

2018

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Natural killer T (NKT) cells are unique unconventional T cells that are reactive to lipid antigens presented on the non-polymorphic major histocompatibility class (MHC) I-like molecule CD1d. They have characteristics of both innate and adaptive immune cells, and have potent immunoregulatory roles in tumor immunity, autoimmunity, and infectious diseases. Based on their T cell receptor (TCR) expression, NKT cells are divided into two subsets, type I NKT cells with an invariant TCRα-chain (Vα24 in humans, Vα14 in mice) and type II NKT cells with diverse TCRs. While type I NKT cells are well-studied, knowledge about type II NKT cells is still limited, and it is to date only possible to identify subsets of this population. However, recent advances have shown that both type I and type II NKT cells play important roles in many inflammatory situations, and can sometimes regulate the functions of each other. Type II NKT cells can be both protective and pathogenic. Here, we review current knowledge on type II NKT cells and their functions in different disease settings and how these cells can influence immunological outcomes.

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“…A recent study has suggested that the ICOS and PD-1 ligand pathways are required for the regulation of T1D in NOD mice by CD4 + type II NKT cells (33). Sulfatide-mediated type II NKT cell activation can also result in IL-10 secretion and, consequently, inhibition of type I NKT cells and diabetogenic or encephalitogenic CD4 + and CD8 + T cells (13, 27).…”

Section: A Novel Type II Nkt Cell-mediated Immune Regulatory Pathwaymentioning

confidence: 99%

Type II NKT Cells in Inflammation, Autoimmunity, Microbial Immunity, and Cancer

2015

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Natural killer T cells (NKT) recognize self and microbial lipid antigens presented by non-polymorphic CD1d molecules. Two major NKT cell subsets, type I and II, express different types of antigen receptors (TCR) with distinct mode of CD1d/lipid recognition. Though type II NKT cells are less frequent in mice and difficult to study, they are predominant in human. One of the major subsets of type II NKT cells reactive to the self-glycolipid sulfatide is the best characterized and has been shown to induce a dominant immune regulatory mechanism that controls inflammation in autoimmunity and in anti-cancer immunity. Recently, type II NKT cells reactive to other self-glycolipids and phospholipids have been identified suggesting both promiscuous and specific TCR recognition in microbial immunity as well. Since the CD1d pathway is highly conserved, a detailed understanding of the biology and function of type II NKT cells as well as their interplay with type I NKT cells or other innate and adaptive T cells will have major implications for potential novel interventions in inflammatory and autoimmune diseases, microbial immunity, and cancer.

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CD4+ Type II NKT Cells Mediate ICOS and Programmed Death-1–Dependent Regulation of Type 1 Diabetes

Cited by 48 publications

References 54 publications

Dendritic Cells and Anergic Type I NKT Cells Play a Crucial Role in Sulfatide-Mediated Immune Regulation in Experimental Autoimmune Encephalomyelitis

Dendritic Cells and Anergic Type I NKT Cells Play a Crucial Role in Sulfatide-Mediated Immune Regulation in Experimental Autoimmune Encephalomyelitis

Type II NKT Cells: An Elusive Population With Immunoregulatory Properties

Type II NKT Cells in Inflammation, Autoimmunity, Microbial Immunity, and Cancer

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