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T lymphocyte populations within the lamina propria
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Thomas T. MacDonald, Antonio Di Sabatino
As the name says, natural killer T (NKT) cells share phenotypic and functional features with both conventional NK cells and T cells, such as the expression of NK1.1/CD161, Ly49 and NKG2, CD3 and an αβ TCR. NKT cells are characterized by a relatively limited TCR usage. Type I NKT cells in mice express the evolutionarily conserved invariant TCRα chain Vα14-Jα18 associated with a limited set of β chains, Vβ8.2, Vβ7, and Vβ2 segments. Human type I NKT cells express the invariant TCRα chain Vα24-Jα18 paired with Vβ11. Type II (nonclassical) NKT cells in mice and man tend to use diverse α and β chains. Type I NKT cells can be double negative or CD4+ in mice, and in humans, can be CD4+, CD8+, or double negative. All murine and human type I NKT cells but not type II cells bind the glycolipid α-galactosylceramide, NKT cells recognize glycolipids via the MHC-I like molecules CD1. In humans there are five CDI molecules (CD1a–e) with CD1d the best investigated. Mice only express CD1d.
Monocyte and lymphocyte membrane markers: Ontogeny and clinical significance
Published in Gabriel Virella, Medical Immunology, 2019
Scott Sugden, Damien Montamat-Sicotte, Karen K. Yam, Joseph Murphy, Bader Yassine Diab, Virginia Litwin
Group 1 NKT cells recognize antigens presented in the context of the molecules CD1a, CD1b, and CD1c. CD1a is expressed at high levels in the skin epidermis and on Langerhans cells, CD1b on mDCs, and CD1c on B cells. CD1d is expressed by a broad variety of APC. The group 1 NKT cells therefore seem to act in cell-type/tissue-specific antigen recognition, perhaps as a means of providing tissue-specific immune responses. Many Group 1 CD1-restricted T cells are autoreactive, with IL-22-producing CD1a autoreactive T cells.
Nail psoriasis
Published in Archana Singal, Shekhar Neema, Piyush Kumar, Nail Disorders, 2019
Natural killer (NK) cells play an important role in psoriasis pathogenesis by releasing cytokines such as IFN-γ, TNF, and IL-22. NKT cells are a heterogeneous group of innate cells sharing some features of both NK cells and T cells. CD1d, an invariant stimulator of NKT cells, is abundantly expressed in psoriatic epidermis.8 In psoriasis lesions, abundant IL-23 is available from dendritic cells and macrophages. It is required for the expansion and survival of T cells that produce IL-17. Langerhans cells (immature dendritic cells) are also found in abundance in skin lesions of psoriasis.9,10
Phospholipid metabolites of the gut microbiota promote hypoxia-induced intestinal injury via CD1d-dependent γδ T cells
Published in Gut Microbes, 2022
Yuyu Li, Yuchong Wang, Fan Shi, Xujun Zhang, Yongting Zhang, Kefan Bi, Xuequn Chen, Lanjuan Li, Hongyan Diao
Specifically, γδ T cells can be recognized and activated by lipid antigens presented by CD1d, a nonpolymorphic major histocompatibility class (MHC) I-like molecule.19 CD1d molecules are mainly expressed on the surface of antigen-presenting cells, hepatocytes and intestinal epithelial cells.20–23 Sulfatide, a lipid antigen, in the blood can be presented to a specific subset of γδ T cells through CD1d on the surface of antigen-presenting cells.24 Exogenous lipid antigens such as phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) in the liver can also be presented to γδ T cells or natural killer T (NKT) cells through CD1d expressed by hepatocytes to promote activation.22,25–27 Moreover, γδ T cells in the mouse intestine can respond to lipid antigens presented by CD1d, including PE, PG and phosphatidylcholine (PC).23 Since the intestines constantly encounter lipid antigens derived from the commensal microbiota and acute hypoxia can significantly change the gut microbiota composition and structure, we speculate that lipid antigens derived from the intestinal microbiota may be related to the host immune response after acute hypoxia.
Intratumoural administration of an NKT cell agonist with CpG promotes NKT cell infiltration associated with an enhanced antitumour response and abscopal effect
Published in OncoImmunology, 2022
Kef K Prasit, Laura Ferrer-Font, Olivia K Burn, Regan J Anderson, Benjamin J Compton, Alfonso J Schmidt, Johannes U Mayer, Chun-Jen J Chen, Nathaniel Dasyam, David S Ritchie, Dale I Godfrey, Stephen R Mattarollo, P Rod Dunbar, Gavin F Painter, Ian F Hermans
To assess the role of NKT cells further, three different approaches to blocking NKT cell function were used. In the first approach, a CD1d-blocking antibody was administered to mice undergoing treatment. This was initiated 3 days after intratumoural α-GalCer administration to avoid blocking any early NKT cell-mediated APC activation events, so that the analysis was focussed on the role of NKT cells in the later effector phase of the response. In the second approach, analysis was conducted in CD1d deficient (CD1d−/−) animals that are devoid of all CD1d-restricted T cells, including the type I NKT cells known to be α-GalCer-reactive. Finally, analysis was conducted in mice that lack the ability to form the TCR-α chain expressed by type I NKT cells, yet otherwise retain an intact TCR repertoire (Traj18−/−),34 and so were devoid of α-GalCer-reactive cells. All analyses were conducted in mice with E.G7-OVA tumours on each flank, with only one subjected to treatment.
Nanovaccine administration route is critical to obtain pertinent iNKt cell help for robust anti-tumor T and B cell responses
Published in OncoImmunology, 2020
Yusuf Dölen, Michael Valente, Oya Tagit, Eliezer Jäger, Eric A. W. Van Dinther, N. Koen van Riessen, Martin Hruby, Uzi Gileadi, Vincenzo Cerundolo, Carl G. Figdor
iNKT cells comprise a subset of T cells that share both NK cell characteristics and bear an invariant αβ T cell receptor. Instead of protein peptides that are recognized by regular T cells, iNKT cells recognize glycolipids presented by MHC Class I like molecule CD1d. In particular, microorganism-derived glycolipids that contain a sugar α-linked to a lipid tail are amongst the strongest TCR binding antigens.1 iNKT cells can be divided into further subsets based on their cytokine secretion profile: iNKT1 cells are the only producers of IFN-y, iNKT2 cells mainly produce IL-4 and iNKT17 cells are the sole producers of IL-17.2 iNKT cells have been considered as a potential tool in cancer immunotherapy, making use of their ability to either directly kill tumor cells or to activate NK cells via IFN-y and IL-21 secretion.3,4 Furthermore, it has been demonstrated that iNKT cells exert a strong helper function by the secretion of cytokines to generate robust CD8+ T cell responses.5 Therefore, α-galactosylceramide (α-GalCer) and its analogs thereof have been widely explored as vaccine adjuvants to boost T cell responses.6 In this study, we used IMM60 as an iNKT cell agonist as it was shown to have a higher affinity to human iNKT-cell TCR than α-GalCer and results in extended responses both in human and mouse iNKT cells7