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CD4 T helper

Seung Min Jung, Youngkyun Kim, Juryun Kim, Hyerin Jung, Hyoju Yi, Yeri Alice Rim, Narae Park, Seung Ki Kwok, Sung Hwan Park, Ji Hyeon Ju
PURPOSE: Sodium chloride (NaCl) has been proposed as a driving factor in autoimmune diseases through the induction of pathogenic CD4+ T helper cells that produce interleukin-17 (Th17 cells). This study investigated the effects of NaCl on inflammatory arthritis in mice and humans. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) mice were fed a normal or high-salt diet ad libitum , and clinical and histologic features of arthritis were evaluated. The proportion of Th17 cells in the spleens of CIA mice fed a normal or high-salt diet was evaluated by flow cytometry, and the expression of IL-17 in joints and intestines was determined by immunohistochemical staining...
January 2019: Yonsei Medical Journal
F Ragusa
Sarcoidosis is a systemic inflammatory disease, affecting any organ, and that can be discovered by accident in approximately 5% of cases. High levels of the type-1 helper (Th1)-dependent chemokine, monokine induced by interferon (IFN)-γ (MIG)/chemokine (C-X-C motif) ligand (CXCL)9, and its receptor CXCR3 have been reported in bronchoalveolar lavage and biopsy samples of patients with sarcoidosis. These elevated levels are related with the amount of CD4+ lymphocytes and total lymphocytes. Alveolar macrophages resulted stained positive for all CXCR3 ligands and produced elevated levels of these chemokines...
November 2018: La Clinica Terapeutica
Clément Jacquemin, Alain Taieb, Katia Boniface, Julien Seneschal
Vitiligo is an autoimmune disease characterized by the presence of several autoantibodies, some of which are directed against melanocyte components and have been shown to be associated with the progression of the disease. However, the mechanism involved in the production of autoantibodies remains unclear. Follicular helper CD4+ T cells (TFH) are specialized in B cell activation and antibody production, especially the TFH cell subsets type 2 and type 17. To date, TFH cell subsets have not been studied in human vitiligo...
December 15, 2018: Pigment Cell & Melanoma Research
Jessica A Kotov, Marc K Jenkins
The T follicular helper (Tfh) cell subset of CD4+ Th cells promotes affinity maturation by B cells in germinal centers. The contribution of other Th cell subsets to B cell responses has not been fully explored in vivo. We addressed this issue by analyzing the T cell-dependent B cell response to the protein Ag PE in mice lacking specific Th cell subsets. As expected, PE-specific germinal center B cell production required Tfh cells. However, Tfh, Th1, or Th17 cell-deficient mice produced as many PE-specific, isotype-switched plasmablasts as wild-type mice...
December 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Emily Gage, Neal Van Hoeven, Natasha Dubois Cauwelaert, Sasha E Larsen, Jesse Erasmus, Mark T Orr, Rhea N Coler
Influenza A annually infects 5-10% of the world's human population resulting in one million deaths. Influenza causes annual epidemics and re-infects previously exposed individuals because of antigenic drift in the glycoprotein hemagglutinin. Due to antigenic drift, the immune system is simultaneously exposed to novel and conserved parts of the influenza virus via vaccination and/or infection throughout life. Preexisting immunity has long been known to augment subsequent hemagglutination inhibitory antibody (hAb) responses...
December 12, 2018: European Journal of Immunology
C J Joonè, M L Schulman, G T Fosgate, T A Plagis, J E Crafford, S K Gupta, H J Bertschinger
Few studies have investigated the cell mediated immune response during zona pellucida-based immunocontraception, despite hypothesized cytotoxic T-cell involvement in ovarian dysfunction associated with these vaccines. This study aimed to investigate antigen-specific anamnestic responses of helper (CD4+ ) and cytotoxic (CD8+ ) T-lymphocytes in peripheral blood mononuclear cells (PBMC) isolated from pony mares before and after their treatment with native porcine zona pellucida (pZP), recombinant pZP3 and pZP4 antigens (reZP) or adjuvanted saline...
December 5, 2018: Theriogenology
Delphine Planas, Jean-Pierre Routy, Petronela Ancuta
PURPOSE OF THE REVIEW: This review highlights current knowledge on the dichotomous role played by T helper 17 cells (Th17)-polarized CD4 T cells in maintaining mucosal immunity homeostasis versus fueling HIV/simian immunodeficiency virus (SIV) replication/persistence during antiretroviral therapy (ART), with a focus on molecular mechanisms underlying these processes. RECENT FINDING: Th17 cells bridge innate and adaptive immunity against pathogens at mucosal barrier surfaces...
December 12, 2018: Current Opinion in HIV and AIDS
Jun Nakata, Hiroko Nakajima, Hiromu Hayashibara, Kanako Imafuku, Soyoko Morimoto, Fumihiro Fujiki, Daisuke Motooka, Daisuke Okuzaki, Kana Hasegawa, Naoki Hosen, Akihiro Tsuboi, Yoshihiro Oka, Atsushi Kumanogoh, Yusuke Oji, Haruo Sugiyama
In immunotherapy by cancer antigen-derived peptide vaccine, vaccination of cytotoxic T lymphocyte (CTL) peptide alone is common, while it remains unclear whether the addition of helper peptide vaccine to the CTL peptide vaccine is of great advantage for the enhancement of tumor immunity. In the present study, combination vaccine of Wilms' tumor gene 1(WT1) protein-derived CTL and helper peptides induced the strong infiltration of WT1-specific CD8+ T cells into mouse tumor at frequencies of 8.8%, resulting in the formation of multiple microscopic necrotic lesions in the tumor, whereas the frequencies of WT1-specific CD8+ T cell infiltration into the tumor in the vaccination of the CTL peptide alone were only 0...
November 13, 2018: Oncotarget
Tatiana M Garcia-Bates, Mariana L Palma, Chengli Shen, Andrea Gambotto, Bernard J C Macatangay, Robert L Ferris, Charles R Rinaldo, Robbie B Mailliard
Eliciting highly functional CD8+ cytotoxic T lymphocyte (CTL) responses against a broad range of epitopes will likely be required for immunotherapeutic control of HIV-1 infection. However, the combination of CTL exhaustion and the ability of HIV-1 to rapidly establish CTL escape variants represent major hurdles towards this goal. Our previous work highlighted the use of monocyte derived, mature, high IL-12-producing type-1 polarized dendritic cells (MDC1) to selectively induce more potent effector CTLs derived from naïve, rather than memory, CD8+ T cell precursors isolated from HIV-1 positive participants in the Multicenter AIDS Cohort Study...
December 12, 2018: Journal of Virology
Anne S Dejean, Emeline Joulia, Thierry Walzer
Eomesodermin (Eomes) is a transcription factor (TF) of the T-box family closely related to T-bet known for its role in CD8 T cell and natural killer cell differentiation. However, the role of Eomes in CD4 T-cell differentiation is less well appreciated. In this issue of the European Journal of Immunology [Eur. J. Immunol. 2019. 49: XXXX-XXXX] Mazzoni et al. and Gruarin et al. studied the role of Eomes in human CD4 T-cell differentiation. Mazzoni et al. showed that Eomes plays a key role in helper T cell (Th) plasticity by favoring the phenotype shift of Th17 cells towards non-classic Th1 cells; while Gruarin et al...
December 7, 2018: European Journal of Immunology
Alexander M Saucedo, Jorge De La Cerda, Hiroo Suami, Rita E Serda
Beyond heterogeneous cancer cells, the tumor microenvironment includes stromal and immune cells, blood vessels, extracellular matrix and biologically active molecules. Abnormal signaling, uncontrolled proliferation and high interstitial pressure all contribute to a chaotic, non-hierarchical vascular organization. Using an immune competent 4T1 breast adenocarcinoma murine model, this study fully characterizes the architecture and immunocyte milieu of the tumor microenvironment. Heterogeneous vessel distribution, chaotic connectivity, limited perfusion, cancer cell density, immune phenotype, and biological responses to immune therapy are presented...
December 3, 2018: Biomedical Microdevices
Suzanne Furlong, Melanie R Power Coombs, Javad Ghassemi-Rad, David W Hoskin
Thy-1 (CD90) is a glycosylphosphatidylinositol-anchored protein (GPI-AP) with signaling properties that is abundant on mouse T cells. Upon antibody-mediated crosslinking, Thy-1 provides a T cell receptor (TcR)-like signal that is sufficient to drive CD4+ T cell proliferation and differentiation into effector cells when costimulatory signals are provided by syngeneic lipopolysaccharide-matured bone marrow-derived dendritic cells. In this study, we investigated the impact of Thy-1 signaling on the production of the T helper (Th) cell subset-associated cytokines, interferon (IFN) γ, interleukin (IL)-4 and IL-17A, as well as the in vitro polarization of highly purified resting CD4+ T cells into Th1, Th2, and Th17 cells...
2018: Frontiers in Cell and Developmental Biology
Kaiting Yang, Yong Liang, Zhichen Sun, Longchao Liu, Jing Liao, Hairong Xu, Mingzhao Zhu, Yang-Xin Fu, Hua Peng
Though lymphotoxin (LT) is highly expressed by type I helper T (Th1) cells, its contribution to CD4+ T cell differentiation during infections and diseases remains a mystery. In HSV-1 infection, we observed that LTβR signaling is required to limit the Th1 response. Using bone marrow chimeric mice, mixed-T-cell chimeric mice, and LTβR in vivo blockades, we unexpectedly observed that LT, especially T cell-derived LT, played an indispensable role in limiting the Th1 response. The LTβR-Ig blockade promoted the Th1 response by increasing infiltration of monocytes and monocyte-derived DCs and up-regulating IL-12 secretion in the lymphoid environment...
December 7, 2018: Scientific Reports
M Saeed Qureshi, Jawaher Alsughayyir, Manu Chhabra, Jason M Ali, Martin J Goddard, Chris Devine, Thomas M Conlon, Michelle A Linterman, Reza Motallebzadeh, Gavin J Pettigrew
The development of humoral autoimmunity following organ transplantation is increasingly recognised, but of uncertain significance. We examine whether autoimmunity contributes independently to allograft rejection. In a MHC class II-mismatched murine model of chronic humoral rejection, we report that effector antinuclear autoantibody responses were initiated upon graft-versus-host allorecognition of recipient B cells by donor CD4 T-cells transferred within heart allografts. Consequently, grafts were rejected more rapidly, and with markedly augmented autoantibody responses, upon transplantation of hearts from donors previously primed against recipient...
December 6, 2018: Journal of Autoimmunity
Katherine A Riccione, Li-Zhen He, Peter E Fecci, Pamela K Norberg, Carter M Suryadevara, Adam Swartz, Patrick Healy, Elizabeth Reap, Tibor Keler, Qi-Jing Li, Kendra L Congdon, Luis Sanchez-Perez, John H Sampson
Despite their promise, tumor-specific peptide vaccines have limited efficacy. CD27 is a costimulatory molecule expressed on CD4+ and CD8+ T cells that is important in immune activation. Here we determine if a novel CD27 agonist antibody (αhCD27) can enhance the antitumor T cell response and efficacy of peptide vaccines. We evaluated the effects of αhCD27 on the immunogenicity and antitumor efficacy of whole protein, class I-restricted, and class II-restricted peptide vaccines using a transgenic mouse expressing human CD27...
2018: Oncoimmunology
Ya-Nan Du, Xiao-Feng Tang, Lian Xu, Wen-Dong Chen, Ping-Jin Gao, Wei-Qing Han
It has been demonstrated that serum/glucocorticoid regulated kinase 1 (SGK1) and the downstream transcription factor forkhead box O1 (FoxO1) plays a critical role in the differentiation of T helper 17 cells/regulatory T cells (Th17/Treg). In the present study, we hypothesized that this SGK1-FoxO1 signaling pathway is involved in Th17/Treg imbalance and target organ damage in angiotensin II (AngII)-induced hypertensive mice. Results show that SGK1 inhibitor EMD638683 significantly reversed renal dysfunction and cardiac dysfunction in echocardiography as indicated by decreased blood urine nitrogen and serum creatinine in AngII-infused mice...
2018: Frontiers in Physiology
Rui Jiang, Yaping Jiang, Ping Xia, Guangwei Luo, Wei Huang, Zhimin Hu, Guilian Cheng, Yin Xiong, Yueqin Wang, Tianpen Cui
Smoking is considered to be the main source of indoor pollution, and it has been identified as an important environmental factor contributing to asthma onset. We know that T helper 2 (Th2) response plays a crucial role in the process of asthma disease. We have investigated the reaction of cigarette smoke extract (CSE) on Th polarization which is controlled by dendritic cells (DCs). Stimulated by CSE, immature DCs from murine bone marrow showed upregulated levels of TIM4. Cocultured with CD4+ T cells, stimulated DCs increased the ratio of IL-4+ versus IFN-γ+ of CD4+ T cells...
December 6, 2018: International Archives of Allergy and Immunology
Shirdi E Schmiel, Lokesh A Kalekar, Na Zhang, Thomas W Blankespoor, Londyn J Robinson, Daniel L Mueller
OBJECTIVE: CD4 germinal center (GC)-T follicular helper (Tfh) cells are important in the pathogenesis of autoimmune arthritis. Previous studies have shown that adenosine 2a receptor (A2aR, Adora2a) signaling can divert CD4 T cells away from the GC-Tfh cell lineage during the primary response to foreign antigens. Therefore, we examined the effects of A2aR signaling on CD4 T cells during the recognition of a self-antigen using a mouse model of autoimmune arthritis. METHODS: Wild type and Adora2a-deficient KRN TCR-transgenic CD4 T cells specific for glucose-6-phosphate isomerase (GPI)/I-Ag7 were transferred into immunodeficient Tcra-/- I-Ag7 -expressing mice to induce arthritis...
December 5, 2018: Arthritis & Rheumatology
Ding-Hong Wu, Miao-Miao Zhang, Ning Li, Xiong Li, Quan-Wei Cai, Wan-Lin Yu, Li-Ping Liu, Wei Zhu, Chuan-Jian Lu
The IL-17-producing CD4+ T cell and γδT cells play critical roles in the pathogenesis of psoriasis (PS). PSORI-CM02 is a representative herbal formula for the treatment for PS in South China. It was confirmed to improve PS without obvious side effects in the clinic. Here we sought to clarify whether and how PSORI-CM02 regulates T cell differentiation and functions in IMQ-induced psoriasis-like BALB/c mouse model. Mice pre-treated 3 days with PSORI-CM02 significantly alleviated skin inflammation, as reduced in PASI score and classic psoriatic characteristics in pathological sections...
December 1, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Kenzo Ohara, Takayuki Ohkuri, Takumi Kumai, Toshihiro Nagato, Yui Nozaki, Kei Ishibashi, Akemi Kosaka, Marino Nagata, Shohei Harabuchi, Mizuho Ohara, Kensuke Oikawa, Naoko Aoki, Yasuaki Harabuchi, Esteban Celis, Hiroya Kobayashi
The human T cell receptor is capable of distinguishing between normal and post-translationally modified peptides. Because aberrant phosphorylation of cellular proteins is a hallmark of malignant transformation, the expression of the phosphorylated epitope could be an ideal antigen to combat cancer without damaging normal tissues. p53 activates transcription factors to suppress tumors by upregulating growth arrest and apoptosis-related genes. In response to DNA damage, p53 is phosphorylated at multiple sites including Ser33 and Ser37...
2018: Oncoimmunology
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