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      The Many Faces of CD4 + T Cells: Immunological and Structural Characteristics

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          Abstract

          As a major arm of the cellular immune response, CD4 + T cells are important in the control and clearance of infections. Primarily described as helpers, CD4 + T cells play an integral role in the development and activation of B cells and CD8 + T cells. CD4 + T cells are incredibly heterogeneous, and can be divided into six main lineages based on distinct profiles, namely T helper 1, 2, 17 and 22 (Th1, Th2, Th17, Th22), regulatory T cells (Treg) and T follicular helper cells (Tfh). Recent advances in structural biology have allowed for a detailed characterisation of the molecular mechanisms that drive CD4 + T cell recognition. In this review, we discuss the defining features of the main human CD4 + T cell lineages and their role in immunity, as well as their structural characteristics underlying their detection of pathogens.

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          Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.

          Gabriela Bindea, Bernhard Mlecnik, Marie Tosolini … (2013)
          The complex interactions between tumors and their microenvironment remain to be elucidated. Combining large-scale approaches, we examined the spatio-temporal dynamics of 28 different immune cell types (immunome) infiltrating tumors. We found that the immune infiltrate composition changed at each tumor stage and that particular cells had a major impact on survival. Densities of T follicular helper (Tfh) cells and innate cells increased, whereas most T cell densities decreased along with tumor progression. The number of B cells, which are key players in the core immune network and are associated with prolonged survival, increased at a late stage and showed a dual effect on recurrence and tumor progression. The immune control relevance was demonstrated in three endoscopic orthotopic colon-cancer mouse models. Genomic instability of the chemokine CXCL13 was a mechanism associated with Tfh and B cell infiltration. CXCL13 and IL21 were pivotal factors for the Tfh/B cell axis correlating with survival. This integrative study reveals the immune landscape in human colorectal cancer and the major hallmarks of the microenvironment associated with tumor progression and recurrence. Copyright © 2013 Elsevier Inc. All rights reserved.
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            TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells.

            Marc Veldhoen, Richard J Hocking, Christopher J Atkins … (2006)
            We describe de novo generation of IL-17-producing T cells from naive CD4 T cells, induced in cocultures of naive CD4 T cells and naturally occurring CD4+ CD25+ T cells (Treg) in the presence of TLR3, TLR4, or TLR9 stimuli. Treg can be substituted by TGFbeta1, which, together with the proinflammatory cytokine IL-6, supports the differentiation of IL-17-producing T cells, a process that is amplified by IL-1beta and TNFalpha. We could not detect a role for IL-23 in the differentiation of IL-17-producing T cells but confirmed its importance for their survival and expansion. Transcription factors GATA-3 and T-bet, as well as its target Hlx, are absent in IL-17-producing T cells, and they do not express the negative regulator for TGFbeta signaling, Smad7. Our data indicate that, in the presence of IL-6, TGFbeta1 subverts Th1 and Th2 differentiation for the generation of IL-17-producing T cells.
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              Rheumatoid arthritis

              Anne Barton, Kazuhiko Yamamoto, Vibeke Strand … (2018)
              Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that primarily affects the joints and is associated with autoantibodies that target various molecules including modified self-epitopes. The identification of novel autoantibodies has improved diagnostic accuracy, and newly developed classification criteria facilitate the recognition and study of the disease early in its course. New clinical assessment tools are able to better characterize disease activity states, which are correlated with progression of damage and disability, and permit improved follow-up. In addition, better understanding of the pathogenesis of RA through recognition of key cells and cytokines has led to the development of targeted disease-modifying antirheumatic drugs. Altogether, the improved understanding of the pathogenetic processes involved, rational use of established drugs and development of new drugs and reliable assessment tools have drastically altered the lives of individuals with RA over the past 2 decades. Current strategies strive for early referral, early diagnosis and early start of effective therapy aimed at remission or, at the least, low disease activity, with rapid adaptation of treatment if this target is not reached. This treat-to-target approach prevents progression of joint damage and optimizes physical functioning, work and social participation. In this Primer, we discuss the epidemiology, pathophysiology, diagnosis and management of RA.
              Article 0 comments Cited 820 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Mol Sci
                Journal ID (iso-abbrev): Int J Mol Sci
                Journal ID (publisher-id): ijms
                Title: International Journal of Molecular Sciences
                Publisher: MDPI
                ISSN (Electronic): 1422-0067
                Publication date (Electronic): 23 December 2020
                Publication date Collection: January 2021
                Volume: 22
                Issue: 1
                Electronic Location Identifier: 73
                Affiliations
                [1 ]Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; dimitra.chatzileontiadou@ 123456monash.edu (D.S.M.C.); Hannah.Sloane1@ 123456monash.edu (H.S.); andrea.nguyen@ 123456monash.edu (A.T.N.); stephanie.gras@ 123456monash.edu (S.G.)
                [2 ]Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia
                Author notes
                [* ]Correspondence: emma.grant@ 123456monash.edu
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0001-7416-038X
                Article
                Publisher ID: ijms-22-00073
                DOI: 10.3390/ijms22010073
                PMC ID: 7796221
                PubMed ID: 33374787
                SO-VID: 010c3245-b2d8-438d-a578-707acb8fb426
                Copyright © © 2020 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 14 November 2020
                Date accepted : 21 December 2020
                Categories
                Subject: Review

                ScienceOpen disciplines: Molecular biology
                Keywords: cd4 t cell,th1,th2,th17,th22,treg,tfh,human leukocyte antigen (hla),structural biology
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: cd4 t cell, th1, th2, th17, th22, treg, tfh, human leukocyte antigen (hla), structural biology

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