Primary immunodeficiency associated with defects in CD1 and CD1‐restricted T cells

Zeißig, Sebastian; Blumberg, Richard S.

doi:10.1111/j.1749-6632.2011.06380.x

Cited by 15 publications

(12 citation statements)

References 111 publications

(255 reference statements)

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“…Given the central role of NKT cells in immunity to pulmonary and cardiotropic microbial pathogens as well as cancer immunity in mice, these findings support the concept of immunerelated defects due to deficiency in MTP and CD1 (Zeissig et al, 2010; Zeissig and Blumberg, 2012). However, the spectrum of immune defects in ABL is remarkably restricted, which contrasts with observations in CD1d-deficient mice.…”

Section: The Biological Role Of Lipid-reactive T Cells In Human Immunitysupporting

confidence: 69%

Lipid antigens in immunity

Dowds

Kornell

Blumberg

et al. 2013

Biological Chemistry

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Lipids are not only a central part of human metabolism but also play diverse and critical roles in the immune system. As such, they can act as ligands of lipid-activated nuclear receptors, control inflammatory signaling through bioactive lipids such as prostaglandins, leukotrienes, lipoxins, resolvins, and protectins, and modulate immunity as intracellular phospholipid- or sphingolipid-derived signaling mediators. In addition, lipids can serve as antigens and regulate immunity through the activation of lipid-reactive T cells, which is the topic of this review. We will provide an overview of the mechanisms of lipid antigen presentation, the biology of lipid-reactive T cells, and their contribution to immunity.

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Section: The Biological Role Of Lipid-reactive T Cells In Human Immunitysupporting

confidence: 69%

Lipid antigens in immunity

Dowds

Kornell

Blumberg

et al. 2013

Biological Chemistry

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“…The positive staining of Langerhans cells that we observed in the skin was probably because of intracellular accumulation of CD1a molecules in the absence of b 2 m. 40 Although CD1d surface expression appears to be less dependent on b 2 m expression, 41 as described in b 2 m-deficient mice, 42 our patients lacked classical CD1d-dependent invariant natural killer T (iNKT) cells, expanding the spectrum of primary immunodeficiency disorders lacking classical iNKT cells. 43 In patients with b 2 m deficiency, the lack of iNKT cells might be due to impaired intracellular trafficking and glycosylation of CD1d. 41 Neither sibling showed laboratory findings of iron overload as observed in b 2 m-deficient mice because of disturbed expression of hemochromatosis protein.…”

Section: Discussionmentioning

confidence: 99%

β2-Microglobulin deficiency causes a complex immunodeficiency of the innate and adaptive immune system

Ardeniz

Unger

Önay

et al. 2015

Journal of Allergy and Clinical Immunology

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“…Primary immunodeficiencies have provided more obvious clues to the biology of human iNKT cells revealing important and unexpected factors involved in their development, such as SAP, XIAP, and WASP. [10][11][12][13][14] The X-linked lymphoproliferative (XLP) syndrome was the first identified inherited immunodeficiency associated with an iNKT cell defect. The main clinical feature of XLP is a peculiar susceptibility to Epstein-Barr virus (EBV) infection, subsequent hemophagocytic lymphohistiocytosis (HLH), and hypogammaglobulinemia.…”

Section: Introductionmentioning

confidence: 99%

Human iNKT and MAIT cells exhibit a PLZF-dependent proapoptotic propensity that is counterbalanced by XIAP

Gérart

Sibéril

Martin

et al. 2013

Blood

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Key Points• Human innate-like lymphocytes, iNKT and MAIT cells exhibit a proapoptotic phenotype associated with increased levels of caspases.• The proapoptotic feature of iNKT and MAIT cells depends on the transcription factor PLZF and is regulated by the anti-apoptotic factor XIAP. Invariant natural killer (iNKT) T cells and mucosal-associated invariant T (MAIT) cells represent peculiar T-lymphocyte subpopulations with innate-like properties that differ from conventional T cells. iNKT are reduced in the primary immunodeficiency caused by mutations in the X-linked inhibitor of apoptosis (XIAP). By studying the mechanism of this depletion, we herein report that iNKT cells exhibit a high susceptibility to apoptosis that is not observed with conventional T cells. Elevated expression of caspases 3 and 7 accounts for the proapoptotic phenotype of iNKT cells, which is inhibited by XIAP although it exerts a moderate effect in conventional T cells. Similarly, MAIT cells exhibit a proapoptotic propensity with elevated expression of activated caspases and are decreased in XIAP-deficient individuals. Knockdown of the transcription factor PLZF/ ZBTB-16, which is involved in the effector program of iNKT cells, diminishes their proapoptotic phenotype. Conversely, overexpression of PLZF/ZBTB-16 in conventional T cells leads to a proapoptotic phenotype. Our findings identify a previously unknown pathway of regulation of innate-like T-cell homeostasis depending on XIAP and PLZF. The proapoptotic feature of iNKT cells also gives a reliable explanation of their exhaustion observed in different human IntroductionInvariant natural killer T (iNKT) lymphocytes represent a distinct T-cell lineage with innate-like traits differing from conventional T cells. 1 In humans, iNKT cells express an invariant (or semiinvariant in mice) TCR made of the V␣24/J␣18/V␤11 rearrangements, which recognize glycosphingolipids from foreign and self origin presented by the MHC class I-like monomorphic molecule CD1d. 2 Several factors required for the development of iNKT cells but not of conventional T cells have been identified including the SLAM family receptors, the SLAM-associated protein (SAP) and transcription factors, such as NF-B, Egr2, HEB, and PLZF. 3 Functionally, iNKT cells are characterized by their ability to rapidly release large amounts of T helper (Th) type 1 (Th1), Th2, and Th17 cytokines and chemokines when activated. In accordance with these unique features, many studies in mice have demonstrated their involvement in a variety of immune responses and immunopathologic conditions. 1 Recently, a second invariant T-cell subpopulation, the mucosal associated invariant T (MAIT) cells was identified both in humans and mice. [4][5][6] These cells express a semi-invariant TCR made of V␣7.2/J␣33 rearrangements and share with iNKT cells several developmental, functional, and phenotypical features. 7,8 In humans, our knowledge of the biology of iNKT cells is more limited. Indeed, iNKT cells are present in very variable albeit low proportions in con...

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Primary immunodeficiency associated with defects in CD1 and CD1‐restricted T cells

Cited by 15 publications

References 111 publications

Lipid antigens in immunity

Lipid antigens in immunity

β2-Microglobulin deficiency causes a complex immunodeficiency of the innate and adaptive immune system

Human iNKT and MAIT cells exhibit a PLZF-dependent proapoptotic propensity that is counterbalanced by XIAP

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