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T Lymphocytes Biology, Pathogenesis and Therapeutic Applications

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 23585

Special Issue Editor


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Guest Editor
Institute of Fundamental Medicine and Biology, Kazan Federal University, OpenLab, 420008 Kazan, Russia
Interests: immune response; cytotoxic T cells; B cells; antibodies; autoantibodies; cytokines; antibody dependent cytotoxicity; pathogen associated molecular patterns; pathogen recognition receptors
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Special Issue Information

Dear colleagues,

T lymphocytes play a key role in developing adaptive immune responses. Their interaction with various subsets of leukocytes is essential for initiating an immune response, maintaining long-term immunity, as well as regulating immune responses. T lymphocyte proliferation and maintenance are supervised by cytokines, chemokines, and growth factors. Failure to control T lymphocyte proliferation and development could lead to autoimmunity and cancer. Therefore, correcting T lymphocyte function is a popular therapeutic approach aiming to restore T lymphocyte efficacy in autoimmunity and cancers. This includes using T cell expression of the TCR gene with defined specificity for cancer treatment. Monoclonal antibodies are also used for treating T cell leukemia. In recent studies, CAR-T cells demonstrated dramatic efficacy in treating hematological malignancies.

This Special Issue will compile the most recent advances in the field, with an emphasis on enhancing the development of cutting-edge strategies aimed to identify the mechanisms regulating activation, proliferation, and development of T lymphocytes. We especially welcome studies identifying novel T lymphocyte markers for disease diagnosis and treatment. Scientists are invited to submit their original research papers, case reports, clinical trials, and review articles with the following potential list of topics:

  1. Mechanisms of T lymphocytes development, activation, and function in health and pathologies;
  2. The role of cytokines, chemokines, and growth factors in the regulation of T lymphocyte function in health and pathologies;
  3. Gene, cell, and gene-cell technologies as the way to regulate T lymphocyte function and deliver therapeutic results;
  4. Novel markers and approaches for diagnosis and T lymphocyte dysfunction;
  5. Novel therapeutic approaches targeting T lymphocytes;
  6. T cell targeting vaccines.

Dr. Svetlana Khaiboullina

Guest Editor

Dr. Svetlana Khaiboullina
Guest Editor

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Keywords

  • T lymphocyte
  • Cancer
  • Autoimmunity
  • Treatment
  • Diagnosis
  • CAR-T
  • Vaccine
  • Cytokines

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Published Papers (3 papers)

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Review

14 pages, 1089 KiB  
Review
Cytokine Release Syndrome Associated with T-Cell-Based Therapies for Hematological Malignancies: Pathophysiology, Clinical Presentation, and Treatment
by Maria Cosenza, Stefano Sacchi and Samantha Pozzi
Int. J. Mol. Sci. 2021, 22(14), 7652; https://doi.org/10.3390/ijms22147652 - 17 Jul 2021
Cited by 44 | Viewed by 11700
Abstract
Cytokines are a broad group of small regulatory proteins with many biological functions involved in regulating the hematopoietic and immune systems. However, in pathological conditions, hyperactivation of the cytokine network constitutes the fundamental event in cytokine release syndrome (CRS). During the last few [...] Read more.
Cytokines are a broad group of small regulatory proteins with many biological functions involved in regulating the hematopoietic and immune systems. However, in pathological conditions, hyperactivation of the cytokine network constitutes the fundamental event in cytokine release syndrome (CRS). During the last few decades, the development of therapeutic monoclonal antibodies and T-cell therapies has rapidly evolved, and CRS can be a serious adverse event related to these treatments. CRS is a set of toxic adverse events that can be observed during infection or following the administration of antibodies for therapeutic purposes and, more recently, during T-cell-engaging therapies. CRS is triggered by on-target effects induced by binding of chimeric antigen receptor (CAR) T cells or bispecific antibody to its antigen and by subsequent activation of bystander immune and non-immune cells. CRS is associated with high circulating concentrations of several pro-inflammatory cytokines, including interleukins, interferons, tumor necrosis factors, colony-stimulating factors, and transforming growth factors. Recently, considerable developments have been achieved with regard to preventing and controlling CRS, but it remains an unmet clinical need. This review comprehensively summarizes the pathophysiology, clinical presentation, and treatment of CRS caused by T-cell-engaging therapies utilized in the treatment of hematological malignancies. Full article
(This article belongs to the Special Issue T Lymphocytes Biology, Pathogenesis and Therapeutic Applications)
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23 pages, 4167 KiB  
Review
Regulation of T-cell Receptor Gene Expression by Three-Dimensional Locus Conformation and Enhancer Function
by Alonso Rodríguez-Caparrós, Jesús Álvarez-Santiago, María Jesús del Valle-Pastor, Carlos Suñé, Jennifer López-Ros and Cristina Hernández-Munain
Int. J. Mol. Sci. 2020, 21(22), 8478; https://doi.org/10.3390/ijms21228478 - 11 Nov 2020
Cited by 14 | Viewed by 6024
Abstract
The adaptive immune response in vertebrates depends on the expression of antigen-specific receptors in lymphocytes. T-cell receptor (TCR) gene expression is exquisitely regulated during thymocyte development to drive the generation of αβ and γδ T lymphocytes. The TCRα, TCRβ, TCRγ, and TCRδ genes [...] Read more.
The adaptive immune response in vertebrates depends on the expression of antigen-specific receptors in lymphocytes. T-cell receptor (TCR) gene expression is exquisitely regulated during thymocyte development to drive the generation of αβ and γδ T lymphocytes. The TCRα, TCRβ, TCRγ, and TCRδ genes exist in two different configurations, unrearranged and rearranged. A correctly rearranged configuration is required for expression of a functional TCR chain. TCRs can take the form of one of three possible heterodimers, pre-TCR, TCRαβ, or TCRγδ which drive thymocyte maturation into αβ or γδ T lymphocytes. To pass from an unrearranged to a rearranged configuration, global and local three dimensional (3D) chromatin changes must occur during thymocyte development to regulate gene segment accessibility for V(D)J recombination. During this process, enhancers play a critical role by modifying the chromatin conformation and triggering noncoding germline transcription that promotes the recruitment of the recombination machinery. The different signaling that thymocytes receive during their development controls enhancer activity. Here, we summarize the dynamics of long-distance interactions established through chromatin regulatory elements that drive transcription and V(D)J recombination and how different signaling pathways are orchestrated to regulate the activity of enhancers to precisely control TCR gene expression during T-cell maturation. Full article
(This article belongs to the Special Issue T Lymphocytes Biology, Pathogenesis and Therapeutic Applications)
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13 pages, 2154 KiB  
Review
The Effects of Asbestos Fibers on Human T Cells
by Naoko Kumagai-Takei, Suni Lee, Bandaru Srinivas, Yurika Shimizu, Nagisa Sada, Kei Yoshitome, Tatsuo Ito, Yasumitsu Nishimura and Takemi Otsuki
Int. J. Mol. Sci. 2020, 21(19), 6987; https://doi.org/10.3390/ijms21196987 - 23 Sep 2020
Cited by 12 | Viewed by 4972
Abstract
Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos fibers on immunocompetent cells, however, have not been well studied. Asbestos physically comprises a fibrous substance, which differs from silica particles which are a particulate substance, although [...] Read more.
Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos fibers on immunocompetent cells, however, have not been well studied. Asbestos physically comprises a fibrous substance, which differs from silica particles which are a particulate substance, although chemically it is a mineral silicate. Since silicosis patients previously exposed to silica particles often suffer from lung and autoimmune diseases, it is clear that silica exposure impairs immune tolerance. Similarly, asbestos may alter the immune system in asbestos-exposed individuals. Given that malignant tumors can result following exposure to asbestos, the attenuation of anti-tumor immunity in cases of asbestos exposure is an important area of investigation. We observed the effect of asbestos fibers on T lymphocytes, such as CD8+ cytotoxic T lymphocytes (CTLs), CD4+ helper T (Th), and regulatory T (Treg) cells, and showed that anti-tumor immunity was attenuated, as demonstrated in a system that stimulates fresh cells isolated from peripheral blood in vitro and a system that is continuously exposed to a cell line. In this manuscript, we introduce the experiments and results of studies on CTLs, as well as Th and Treg cells, and discuss how future changes in immunocompetent cells induced by asbestos fibers can be clinically linked. Full article
(This article belongs to the Special Issue T Lymphocytes Biology, Pathogenesis and Therapeutic Applications)
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