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Lymphocyte trafficking from inductive sites to effector sites
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Valerie Verhasselt, William Agace, Oliver Pabst, Andrew Stagg
S1P binds to five G-protein-coupled receptors designated S1P1–S1P5. Egress of naive T cells from lymph nodes depends on S1P1, because S1P1-deficient T cells fail to leave lymph nodes. S1P1 is internalized on encountering high S1P concentration such as that found in blood and lymph but is maintained on the cell surface in areas of low S1P concentration such as the lymph nodes. Thus, shuttling of S1P1 between the cell surface and cytosol seems to regulate lymphocyte egress from lymph nodes, and the reappearance of S1P1 on the cell surface during lymph node transit might override retention signals, possibly including CCL21–CCR7 interactions, and initiate lymphocyte egress. After their activation, T cells express the early T-cell activation marker CD69, a transmembrane protein of the C-type lectin family. Association between CD69 and S1P1 induces S1P1 internalization, leading to reduced responsiveness to S1P and inhibition of lymphocyte exit. Later, after extensive proliferation in the lymph node, T cells lose their expression of CD69 and reexpress S1P1; as a consequence, they regain their ability to leave via efferent lymph.
T Cells:Regulation and Cellular Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
This molecule is expressed very soon (two to four hours) following activation of T, B and NK cells, and is also found on platelets, neutrophils and monocytes. CD69 is a disulfide-linked homodimer with each chain having Mr of 26–34 kDa (depending on glycosylation). The physiologic ligand of CD69 has not yet been identified; binding of CD69 increases intracellular calcium and contributes to T (or B) cell activation. Binding of CD69 along with simultaneous activation of protein kinase C by other mechanisms leads to cytokine production and cell proliferation. CD69 appears to trigger calcium-mediated activating mechanisms in all cells which express it.
The Role of Adhesion in Eosinophil Accumulation and Activation in Asthma
Published in Gerald J. Gleich, A. Barry Kay, Eosinophils in Allergy and Inflammation, 2019
Andrew J. Wardlaw, Garry M. Walsh, A. R. E. Anwar, Adele Hartnell, Andrew M. Bentley, A. Barry Kay
Modulation of eosinophil phenotype by cytokines suggests that the profile of leukocyte receptor expression on tissue eosinophils may be very different from that on peripheral blood eosinophils. The receptors involved in triggering eosinophil mediator release at sites of allergic inflammation are still unclear. One possibility is that a receptor whose expression was induced as the eosinophils migrated into the extravascular tissue may be involved. CD69 is a receptor that is induced on T lymphocytes within 2–3 h of activation (27). Perturbation of CD69 with monoclonal antibodies in concert with PMA induced peripheral blood T cells to proliferate. In addition, CD69 is constitutively expressed on platelets, where it acts as a receptor for platelet aggregation and degranulation (28). We found that although peripheral blood eosinophils did not express CD69, within 1–2 h of culture with GM-CSF, CD69 expression on eosinophils was detected. Expression was maximal by 1 day and sustained for at least 2 days (Fig. 7). Expression was dose dependent and induced by GM-CSF but not by PAF. Expression was not inhibited by dexamethasone but was partly inhibited by cyclohexamide. Neutrophils did not express CD69 after culture with GM-CSF. Importantly, BAL eosinophils from asthmatics expressed similar amounts of CD69 to in vitro GM-CSF-stimulated peripheral blood eosinophils, confirming the in vivo relevance of this observation.
Melanoma patients with immune-related adverse events after immune checkpoint inhibitors are characterized by a distinct immunological phenotype of circulating T cells and M-MDSCs
Published in OncoImmunology, 2023
Alisa Lepper, Rebekka Bitsch, Feyza Gül Özbay Kurt, Ihor Arkhypov, Samantha Lasser, Jochen Utikal, Viktor Umansky
Patients with irAE were reported to show a clonal expansion of CD8+ T cells.33,34 Moreover, it was described an association of circulating activated T cells with the occurrence of irAE.35 In accordance to these data, we found an enrichment of activated CD8+ and CD4+ T cells during irAE indicated by an upregulation of activation markers CD69 and CD25. The increase of CD69 expression has been identified in patients with various inflammatory diseases such as arthritis, autoimmune thyroiditis, or multiple sclerosis.36 A stronger expansion of CD25 and CD69 on CD8+ T cells in patients without irAE compared to patients experiencing musculoskeletal irAE was shown by Benesova et al.37 In contrast to their analysis, we measured the changes of CD25+CD8+ as well as CD69+CD8+ T cells for particular time points: before irAE vs. during irAE.
Determination of suppressive effect on human T-cell activation by hispidulin, nepetin, and vanillic acid
Published in Immunopharmacology and Immunotoxicology, 2019
Premrutai Thitilertdecha, Varangkana Tantithavorn, Poonsin Poungpairoj, Nattawat Onlamoon
Once the cells have been activated, a variety of activation antigens are expressed on their cell surface. CD69 is the earliest expressed antigen on stimulated cells and involves in proliferation and functions as a signal-transmitting receptor in lymphocytes. CD25 is, on the other hand, expressed at the later phase of activation and acts as a signal-transmitting receptor of IL-2 for further T-cell stimulation. CD69 and CD25 are thus used as early activation markers. In order to assess the inhibitory effects of hispidulin, nepetin, and vanillic acid at different concentrations on T-cell activation, it is also necessary to have a control for comparison. 2 mM EDTA was then chosen as a T-cell activation inhibitor due to its complete inhibition in the formation of conjugates between T cells and their target cells [19]. From our preliminary screening in different concentrations of the compounds ranging from 1 to 500 µM, results showed that there had no significant change in activation inhibition when using the concentrations below 50 µM and the compounds were precipitated when preparing the concentration above 200 µM (data not shown). Therefore, the concentrations used in this study are between 50 and 200 µM. DMSO at the maximum volume of 10 µL was also tested to ensure that it does not affect T-cell activation. Results showed that no significant change was found in numbers of viable lymphocytes and activation markers (CD25+ and CD69+) in both CD4+ and CD8+ T cells when compared to the control groups without DMSO (data not shown).
Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5
Published in OncoImmunology, 2019
Yoko Tsukita, Tatsuma Okazaki, Satoru Ebihara, Riyo Komatsu, Mayumi Nihei, Makoto Kobayashi, Taizou Hirano, Hisatoshi Sugiura, Tsutomu Tamada, Nobuyuki Tanaka, Yasufumi Sato, Hideo Yagita, Masakazu Ichinose
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) belongs to the tumor necrosis factor family.1 Death receptor5 (DR5) is a TRAIL receptor. Its agonistic monoclonal antibody (mAb) MD5-1 exerted potent anti-tumor effects in mice,2–4 and DR5 targeting mAbs is now under clinical trials.5 MD5-1 induces apoptosis in TRAIL-sensitive tumor cells when crosslinked. For crosslinking, Fc receptor-expressing immune cells, including natural killer (NK) cells, macrophages, and dendritic cells (DCs), are required. APCs, including macrophages and DCs, play a central role in the crosslinking of MD5-1.2 After the induction of apoptosis, APCs such as DCs incorporate apoptotic cells coated by MD5-1. These APCs migrate to draining lymph nodes (LNs) via lymphatics. In LNs, APCs develop tumor-specific cytotoxic T lymphocytes.1 Thus, in addition to inducing apoptosis in tumor cells, MD5-1 induces tumor-specific effector and memory T cells.1 The anti-tumor effects of MD5-1 were largely APC and T cell dependent.2 To promptly induce tumor-specific cytotoxic T lymphocytes, the activation of APCs is necessary.1 The activated DCs enhance the expression of co-stimulatory molecules such as CD80 and CD86.6,7 Activated T cells enhance the expression of CD69.8