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Cells
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Human T Cell Responses in Human Health and Disease
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Human T Cell Responses in Human Health and Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 22510

Special Issue Editor

Prof. Dr. Christina Zielinski

E-Mail Website1 Website2
Guest Editor
Infection Immunology, Leibniz Institute for Natural Product Research and Infection Biology, 07743 Jena, Germany
Interests: T cells; tissue resident memory T cells (TRM); skin immunology; Th17 cells; IL-10
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Over the last few years, the research area of human immunology has been shaped by several novel concepts and technological advances, which have significantly contributed to translational progress in human health. Single-cell technologies, most importantly, single-cell transcriptomics, have entered human immunology and provided more insights into the heterogeneity of lymphocyte populations, thus unmasking novel players in disease pathogenesis and their respective phenotypes, functions and regulatory checkpoints.

Investigations in the area of human immunology have also shifted from the blood to the peripheral tissues. It has been acknowledged that 98% of human T cells reside in peripheral tissues, where they adapt to their local microenvironments and where they assume specialized functions. Their identity has been overlooked by a previous focus on the circulating blood compartment. We now consider these tissue-resident T cells (TRM) to be critical for host defence, cancer and autoimmunity. While great insights have been generated into TRM cells in mouse models, insights into their identity in humans are just beginning to emerge. Considering their impact on human diseases, novel therapeutic strategies are expected to shape medicine in the near future.

While previous years of human T cell research have centred on T cell stability versus plasticity and on cytokine networks, we now consider T cells to be more malleable with a multitude of external signals from the microenvironment. This includes not only their microbial antigens but also metabolites and even ionic signals.

Taken together, human immunology has entered the centre stage in translational research due to its great impact on human health and disease. This Special Issue invites you to share your expertise in this research topic.

Prof. Dr. Christina Zielinski
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • T cells
  • tissue-resident memory
  • autoimmunity
  • cytokines
  • single-cell RNAseq
  • flow cytometry
  • human immunology

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Related Special Issue

Published Papers (4 papers)

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Research

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19 pages, 2572 KiB  
Article
Alpha-Linolenic Acid Modulates T Cell Incorporation in a 3D Tissue-Engineered Psoriatic Skin Model
by Sophie Morin, Mélissa Simard, Geneviève Rioux, Pierre Julien and Roxane Pouliot
Cells 2022, 11(9), 1513; https://doi.org/10.3390/cells11091513 - 30 Apr 2022
Cited by 15 | Viewed by 3402
Abstract
Psoriasis is an autoimmune skin disease with an increased number of leukocytes infiltrating the dermal and epidermal compartments compared with normal skin. N-3 polyunsaturated fatty acids (n-3 PUFAs) are frequently used in the clinic in order to attenuate the symptoms of psoriasis. For [...] Read more.
Psoriasis is an autoimmune skin disease with an increased number of leukocytes infiltrating the dermal and epidermal compartments compared with normal skin. N-3 polyunsaturated fatty acids (n-3 PUFAs) are frequently used in the clinic in order to attenuate the symptoms of psoriasis. For psoriatic patients, a supplementation of the diet with alpha-linolenic acid (ALA) reduces the activation of T cell signaling pathways, leading to a significant reduction in inflammatory cytokine secretion. However, the precise mechanism of action of n-3 PUFAs in psoriasis is still not understood. In the present study, we elucidated the bioaction of ALA on the adaptive immune component of psoriasis by using a psoriatic skin model produced with the addition of activated T cells. Healthy and psoriatic skin substitutes were produced according to the self-assembly method, using culture media supplemented with 10 μM of ALA. T cells were isolated from blood samples using a negative selection isolation method. ALA supplementation regulated the hyperproliferation and abnormal cell differentiation of psoriatic keratinocytes stimulated by T cells. Additionally, the exogenous ALA was correctly incorporated into the phospholipids of keratinocytes, which resulted in increased levels of ALA, eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (n-3 DPA). The infiltration of T cells into the epidermis was reduced when ALA was added to the culture medium, and significant decreases in the levels of inflammatory cytokines and chemokines such as CXCL1, interleukin-6 (IL-6) and interleukin-8 (IL-8) were consequently measured in psoriatic substitutes supplemented with this n-3 PUFA. Altogether, our results showed that in this psoriatic skin model enriched with T cells, ALA exerted its beneficial effect by decreasing the quantities of inflammatory mediators released by T cells. Full article
(This article belongs to the Special Issue Human T Cell Responses in Human Health and Disease)
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15 pages, 2643 KiB  
Article
Increased Frequency of CD4+ Follicular Helper T and CD8+ Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis
by Dornatien Chuo Anang, Tamara H. Ramwadhdoebe, Janine S. Hähnlein, Bo van Kuijk, Noortje Smits, Krijn P. van Lienden, Mario Maas, Daniëlle M. Gerlag, Paul P. Tak, Niek de Vries and Lisa G. M. van Baarsen
Cells 2022, 11(7), 1104; https://doi.org/10.3390/cells11071104 - 24 Mar 2022
Cited by 14 | Viewed by 4329
Abstract
Follicular T helper cells (Tfh cells) provide key B-cell help and are essential in germinal center formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA), we analyzed their frequencies, phenotypes, and cytokine [...] Read more.
Follicular T helper cells (Tfh cells) provide key B-cell help and are essential in germinal center formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA), we analyzed their frequencies, phenotypes, and cytokine profiles in peripheral blood and lymph node biopsies of healthy controls (HCs), autoantibody-positive individuals at risk for developing RA (RA-risk individuals), and early RA patients. Subsequently, we confirmed their presence in lymph nodes and synovial tissue of RA patients using immunofluorescence microscopy. In the blood, the frequency of Tfh cells did not differ between study groups. In lymphoid and synovial tissues, Tfh cells were localized in B-cell areas, and their frequency correlated with the frequency of CD19+ B cells. Compared to lymphoid tissues of healthy controls, those of RA patients and RA-risk individuals showed more CD19+ B cells, CD4+CXCR5+ follicular helper T cells, and CD8+CXCR5+ follicular T cells. These Tfh cells produced less IL-21 upon ex vivo stimulation. These findings suggest that Tfh cells may present a novel rationale for therapeutic targeting during the preclinical stage of RA to prevent further disease progression. Full article
(This article belongs to the Special Issue Human T Cell Responses in Human Health and Disease)
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Review

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13 pages, 1273 KiB  
Review
T-Cell Receptor Repertoire Analysis with Computational Tools—An Immunologist’s Perspective
by Mahima Arunkumar and Christina E. Zielinski
Cells 2021, 10(12), 3582; https://doi.org/10.3390/cells10123582 - 18 Dec 2021
Cited by 11 | Viewed by 10356
Abstract
Over the last few years, there has been a rapid expansion in the application of information technology to biological data. Particularly the field of immunology has seen great strides in recent years. The development of next-generation sequencing (NGS) and single-cell technologies also brought [...] Read more.
Over the last few years, there has been a rapid expansion in the application of information technology to biological data. Particularly the field of immunology has seen great strides in recent years. The development of next-generation sequencing (NGS) and single-cell technologies also brought forth a revolution in the characterization of immune repertoires. T-cell receptor (TCR) repertoires carry comprehensive information on the history of an individual’s antigen exposure. They serve as correlates of host protection and tolerance, as well as biomarkers of immunological perturbation by natural infections, vaccines or immunotherapies. Their interrogation yields large amounts of data. This requires a suite of highly sophisticated bioinformatics tools to leverage the meaning and complexity of the large datasets. Many different tools and methods, specifically designed for various aspects of immunological research, have recently emerged. Thus, researchers are now confronted with the issue of having to choose the right kind of approach to analyze, visualize and ultimately solve their task at hand. In order to help immunologists to choose from the vastness of available tools for their data analysis, this review addresses and compares commonly used bioinformatics tools for TCR repertoire analysis and illustrates the advantages and limitations of these tools from an immunologist’s perspective. Full article
(This article belongs to the Special Issue Human T Cell Responses in Human Health and Disease)
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13 pages, 1091 KiB  
Review
Regulation of T Cell Responses by Ionic Salt Signals
by Christina E. Zielinski
Cells 2021, 10(9), 2365; https://doi.org/10.3390/cells10092365 - 9 Sep 2021
Cited by 6 | Viewed by 3191
Abstract
T helper cell responses are tailored to their respective antigens and adapted to their specific tissue microenvironment. While a great proportion of T cells acquire a resident identity, a significant proportion of T cells continue circulating, thus encountering changing microenvironmental signals during immune [...] Read more.
T helper cell responses are tailored to their respective antigens and adapted to their specific tissue microenvironment. While a great proportion of T cells acquire a resident identity, a significant proportion of T cells continue circulating, thus encountering changing microenvironmental signals during immune surveillance. One signal, which has previously been largely overlooked, is sodium chloride. It has been proposed to have potent effects on T cell responses in the context of autoimmune, allergic and infectious tissue inflammation in mouse models and humans. Sodium chloride is stringently regulated in the blood by the kidneys but displays differential deposition patterns in peripheral tissues. Sodium chloride accumulation might furthermore be regulated by dietary intake and thus by intentional behavior. Together, these results make sodium chloride an interesting but still controversial signal for immune modulation. Its downstream cellular activities represent a potential therapeutic target given its effects on T cell cytokine production. In this review article, we provide an overview and critical evaluation of the impact of this ionic signal on T helper cell polarization and T helper cell effector functions. In addition, the impact of sodium chloride from the tissue microenvironment is assessed for human health and disease and for its therapeutic potential. Full article
(This article belongs to the Special Issue Human T Cell Responses in Human Health and Disease)
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