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Overview of Immune Tolerance Strategies
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Charles J. Hackett, Helen Quill
Another distinct regulatory population, the NKT cells, bears surface molecules commonly found on both natural killer cells and T cells.14,15 NKT cells produce interleukin-4 (IL-4), IL-10, and interferon-gamma, probably influencing the activation of other regulatory T cell populations. NKT cells recognize the APC surface molecule CD1, which presents lipid antigens, in contrast to the peptide-presenting MHC class I or class II molecules.16 Recently, a ligand that is recognized by NK T cells in a CD 1-restricted manner, alpha-galactosylceramide, was shown to protect against the onset of type 1 diabetes in an NOD mouse model.17, 18 Analyses showed that IL-10 production by NKT cells was responsible for the protective effect.
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
NKT cells express a semi-invariant form of the αβ TCR receptors (TCR2) along with NK cell markers such as CD56 and various KIR molecules. They recognize glycolipid antigens presented in association with CD1. NKT cells are thought to play an important role in tumor immunity and immunoregulation. NKT cells can be separated into two groups based on ligand usage.
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
Reconciling two opposing effects of radiation therapy: stimulation of cancer cell invasion and activation of anti-cancer immunity
Published in International Journal of Radiation Biology, 2023
In addition to Treg cells, MDSCs and macrophages, a subgroup of CD8+ natural killer T cells (NKT), has demonstrated a tendency to promote development of distant metastases when their activity is lower in patients with head and neck cancer treated with RT (Schantz and Goepfert 1987). This observation was based on pretreatment circulating levels of NKT cells. Similar to T cells, NKT cells can specialize into an effector-like phenotype that promotes tumor regression or into an immunosuppressive Treg-like phenotype that promotes immune evasion and tumor progression (Chang et al. 2011; Moreira-Teixeira et al. 2012; Brennan et al. 2013). The conversion to immunosuppressive Treg-like NKT cells can result from chronic activation of type I NKT cells leading to their downregulation of T cell and NK cell receptors (TCR, NKR) and upregulation of the inhibitory molecules PD-1 and BTLA (B- and T-lymphocyte attenuator) (Parekh et al. 2005; Iyoda et al. 2010). Further investigation into how NKT cells are modulated by RT may provide insight into new therapeutic avenues.
A comparative study on roles of natural killer T cells in two diet-induced non-alcoholic steatohepatitis-related fibrosis in mice
Published in Annals of Medicine, 2022
Shumei Zheng, Wenzhuo Yang, Dongmei Yao, Shanhong Tang, Juanni Hou, Xing Chang
The differentiation and viability of NKT cells are regulated by cytokines. Previous studies have demonstrated that IL-12 significantly reduces NKT cell viability, while IL-15 increases NKT cell viability. Our subsequent efforts were directed to determine the mechanisms by which dietary factors might reduce hepatic NKT cells. The data showed that hepatic production of IL-12 was increased approximately 8-fold by FFD in WT mice than controls (Figure 4(E)) but unchanged by the MCD diet. Repeated injection of α-GalCer elevated hepatic levels of IL-12 by 4-fold in the MCD group but had no effect in the FFD group (Figure 4(E)). The hepatic level of IL-15 was unchanged by both the FFD and MCD diets (1.9 vs. 1.1, p = .100; 5.9 vs. 1.1, p = .051) (Figure 4(F)). The above results suggested that an increase in IL-12 may contribute to the significant depletion of NKT cells in mice.
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
Perhaps the starkest change in immune profile observed with combination treatment was increased frequency of NKT cells in tumours undergoing rejection. While repeated local CpG treatment may create an environment that supports NKT cell infiltration or local proliferation, these cells also accumulated at the distal untreated tumours that underwent regression with the combined treatment. Furthermore, blocking CD1d-NKT cell interactions after the initial α-GalCer-mediated stimulus compromised the abscopal effect more than the local effect, and in NKT cell deficient animals, where only CpG should be active, the weak abscopal effect induced by CpG alone was also compromised. Thus, our studies suggest that NKT cells may contribute to the establishment of effective immunity at the distal sites, even in the absence of an exogenously administered agonist. Expression of KLRG1 was a key feature of the NKT cell clusters in the tumour and dLNs following administration of the combined treatment. It has previously been reported that KLRG1+ NKT cells accumulate as long-lived effectors in the lung following vaccination with α-GalCer-loaded DCs.65 These cells exhibited a limited CDR3β distribution, most likely as the result of clonal expansion, and responded rapidly to re-challenge several weeks to months after first exposure. As the KLRG1+ NKT cells contributed to long-term resistance to tumour challenge, the authors of this earlier work postulated that selective expansion of these cells should be explored as an antitumour therapy. The intratumoural treatment outlined here may have achieved this goal.