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The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
There are various types of T cells. CTLs are responsible for killing infected cells and tumour cells. TH cells perform a range of functions mediated through the action of secreted cytokines. Regulatory T cells (Treg) play a role in inhibiting immune responses and inadequate Treg function may be a factor in autoimmune diseases. T-cell specificity is determined by the TCR (Figure 2.12), which like antibodies, uses combinatorial gene rearrangement to achieve the necessary diversity of receptors. T-cell receptors recognize short peptide fragments presented on the surface of target cells by major histocompatibility complex (MHC) proteins, which are also referred to as human leukocyte antigens (HLAs).
Clinical Applications of Gene Therapy for Immuno-Deficiencies
Published in Yashwant Pathak, Gene Delivery, 2022
Khushboo Faldu, Sakshi Gurbani, Jigna Shah
Regulatory T cells (Tregs) prevent autoimmunity as they control immune response to self-antigens. IPEX syndrome develops due to the defects in transcription factor fork head box P3 (FoxP3) that are essential for the normal development and functioning of Tregs. IPEX syndrome clinically presents itself as eczema, enteropathy, and type I diabetes mellitus. Treatment involves prolonged immunosuppression and alloHSCT, but immune-mediated complications can limit its efficacy [83]. The T-cell approach lacks capability for the generation of an adequate amount of Tregs to improve clinical phenotype [84]. HSC-GT is challenging as FoxP3 expression in HSCs prevents proliferation and differentiation of the stem cells. The SIN-LV vector incorporating the endogenous FoxP3 promoter and regulatory elements has shown favourable results that induced lineage-specific expression in progeny of transduced HSCs [84–86].
Oncogenesis and Metastasis
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Immune checkpoint blockade forms the basis of immunotherapy.PD-L1 (programmed cell death protein ligand 1) on tumour cells.PD-1 (programmed cell death protein 1) on T-cells.PD-L1 and PD-1 binding results in T-cell deactivation.PD-L1 and/or PD-1 inhibitor are used in metastatic bladder/renal cancers.CTLA-4 (cytotoxic T-lymphocyte associated protein 4).Expressed by regulatory T-cells.CTLA-4 inhibitors are used in metastatic renal cancer.Inhibitors restore tumour-specific T-cell immunity.
Peripheral gene signatures reveal distinct cancer patient immunotypes with therapeutic implications for autologous DC-based vaccines
Published in OncoImmunology, 2022
Michal Hensler, Jana Rakova, Lenka Kasikova, Tereza Lanickova, Josef Pasulka, Peter Holicek, Marek Hraska, Tereza Hrnciarova, Pavla Kadlecova, Andreu Schoenenberger, Klara Sochorova, Daniela Rozkova, Ludek Sojka, Jana Drozenova, Jan Laco, Rudolf Horvath, Michal Podrazil, Guo Hongyan, Tomas Brtnicky, Michal J. Halaska, Lukas Rob, Ales Ryska, An Coosemans, Ignace Vergote, Abhishek D. Garg, David Cibula, Jirina Bartunkova, Radek Spisek, Jitka Fucikova
The frequency of CD4+CD25+FoxP3+ regulatory T cells was assessed by flow cytometry using standard procedures. Briefly, peripheral blood mononuclear cells (PBMCs) were stained with CD45-HV500 (BD Biosciences) CD3-A700 (Exbio), CD4-ECD (Beckman Coulter), and CD25-PE (Exbio) conjugates plus Aqua Blue Live/Dead cell viability dye (Life Technologies) (Supplemental Table 3). Thereafter, cells were fixed with fixation/permeabilization buffer (BD Bioscience), permeabilized with permeabilization buffer (BD Bioscience), and incubated with FoxP3-A488 (Thermo Fisher Scientific). Flow cytometry was performed on an LSRFortessa Analyzer (BD), and data were analyzed using FlowJo software (Tree Star, Inc). After excluding dead cells, regulatory T cells were determined as CD45+CD4+CD25+FoxP3+ cells (Supplementary Figure 1).
γδT17/γδTreg cell subsets: a new paradigm for asthma treatment
Published in Journal of Asthma, 2022
Yi-En Yao, Cai-Cheng Qin, Chao-Mian Yang, Tian-Xia Huang
Treg are a kind of T cell subsets that control autoimmunity in vivo. Regulatory T cells can be divided into natural regulatory T cells (nTreg) and induced adaptive regulatory T cells (aTreg or iTreg), such as Th3 and Tr1. In addition, CD8 Treg and NKT cells are closely related to the occurrence of autoimmune diseases since their abnormal expression can lead to autoimmune diseases. Tr1 cells secrete IL-10 and Th3 cells secrete TGF-β, while in 1995, Sakaguchi found that nearly 10% of the peripheral CD4+ T cells in adult mice expressed the IL-2 receptor α chain CD25. Removal of these cells leads to a variety of autoimmune diseases in mice, and reinfusion of these cells can prevent the occurrence of such diseases. In addition, Treg cell activity is affected by many cytokine interactions in the thymus, which is essential for maintaining self-tolerance (81). Therefore we herein refer to these cells as CD4+ CD25+ Treg
The Role of Regulatory T and B Cells in the Etiopathogenesis of Idiopathic Granulomatous Mastitis
Published in Immunological Investigations, 2022
Hulya Ucaryilmaz, Hande Koksal, Ayca Emsen, Naim Kadoglou, John Michael Dixon, Hasibe Artac
The role of regulatory T cells in autoimmune diseases has been one of the most interesting topics recently. Along with understanding the properties and functions of T regulatory cells, this has contributed to an understanding of the pathogenesis of autoimmune diseases and the development of new treatment strategies, especially in standard-therapy resistant diseases (Kailashiya et al. 2019; Wang et al. 2019). Tregs are recognized as a primary cause of autoimmune and inflammatory diseases in humans (Hoeppli et al. 2015). Foxp3+ Tregs express CD25 and CTLA-4 on the cell surface which can cause variety of immunological diseases in situations of numerical and/or functional disorders. That is why, their decrease or increase in number that cause functional alterations allow controlling physiological and pathological immune responses (Rudensky 2011; Sadati et al. 2019). Foxp3 is known as a credible marker of Tregs and the expression of Foxp3 controls Tregs’ development and function. Foxp3 has been shown to be directly associated with the suppressive activities of Tregs (Sun et al. 2014). However, Foxp3 is an activation marker in Teff cells. In our study, while Foxp3 expression was found to be low, Teff cells ratio were detected in high levels in IGM patients. These differences were also observed in patients with remission. The results indicate that CD4 subsets based on CD25 and Foxp3 play a role in IGM and alter the regulation of T cells in this condition.