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t-cell receptor

Marliane Batista Campos, Luciana Vieira do Rêgo Lima, Ana Carolina Stocco de Lima, Thiago Vasconcelos Dos Santos, Patrícia Karla Santos Ramos, Claudia Maria de Castro Gomes, Fernando Tobias Silveira
Leishmania (V.) braziliensis and Leishmania(L.) amazonensis are the most pathogenic agents of American Cutaneous Leishmaniasis in Brazil, causing a wide spectrum of clinical and immunopathological manifestations, including: localized cutaneous leishmaniasis (LCLDTH+/++), borderline disseminated cutaneous leishmaniasis (BDCLDTH±), anergic diffuse cutaneous leishmaniasis (ADCLDTH-), and mucosal leishmaniasis (MLDTH++++). It has recently been demonstrated, however, that while L. (V.) braziliensis shows a clear potential to advance the infection from central LCL (a moderate T-cell hypersensitivity form) towards ML (the highest T-cell hypersensitivity pole), L...
2018: PloS One
Matthew G K Benesch, Iain T K MacIntyre, Todd P W McMullen, David N Brindley
A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironment which promotes cancer growth, immune evasion, metastasis, and treatment resistance...
March 15, 2018: Cancers
Allison M Weis, Raymond Soto, June L Round
The commensal microbiota influences many aspects of immune system regulation, including T cells, but molecular details of how this occurs are largely unknown. Here we review our findings that the microbiota regulates Erdr1, a secreted apoptotic factor, to control T cell survival. Erdr1 is highly upregulated in CD4+ T cells from germfree mice and antibiotic treated animals, and our study shows that Erdr1 is suppressed by the microbiota via Toll-like receptor signaling and MyD88 dependent pathways. Erdr1 functions in an autocrine fashion and promotes apoptosis through the FAS/FASL pathway...
March 15, 2018: Gut Microbes
Keiichi Koizumi, Minako Hoshiai, Nobuyuki Katsumata, Takako Toda, Hiroaki Kise, Yohei Hasebe, Yosuke Kono, Yuto Sunaga, Masashi Yoshizawa, Atsushi Watanabe, Keiko Kagami, Masako Abe, Kanji Sugita
BACKGROUND: The effect of infliximab (IFX) on immune cells has not been fully reported in Kawasaki disease (KD). To investigate the mechanism of IFX in KD, we examined changes in the abundance of CD14+ CD16+ activated monocytes, regulatory T cells (Treg ), and T-helper cell type 17 (Th17) cells following treatment with IFX. METHODS: We collected peripheral blood from patients with intravenous immunoglobulin (IVIG)-resistant KD and analyzed the absolute counts of CD14+ CD16+ monocytes, Treg cells (CD4+ CD25+ FOXP3+ ) and Th17 cells (CD4+ IL-17A+ ) by flow cytometry...
March 15, 2018: Pediatrics International: Official Journal of the Japan Pediatric Society
Amanda Przespolewski, Andras Szeles, Eunice S Wang
Evasion of the host immune system is a key mechanism to promote malignant progression. Therapeutically targeting immune pathways has radically changed the treatment paradigm for solid and lymphoid tumors but has yet to be approved for myeloid malignancies. Here, we summarize the most recent advances in immunotherapy for acute myeloid leukemia. Topics reviewed here include adoptive cellular approaches (chimeric antigen receptor-T cells, natural killer and other immune cells), checkpoint inhibitors (anti-PD-1/PD-L1, anti-CTLA-4 and TIM-3) and vaccines (WT-1, HLA-A2 and hTERT)...
March 15, 2018: Future Oncology
Lucía Fernández, Alejandra Leivas, Jaime Valentín, Adela Escudero, Dolores Corral, Raquel de Paz, Maria Vela, David Bueno, Rebeca Rodríguez, Juan Manuel Torres, Mariana Díaz-Almirón, Eduardo López-Collazo, Joaquin Martinez-Lopez, Antonio Pérez-Martínez
BACKGROUND: Cancer immunotherapy involving natural killer (NK) cells has gained interest. Here we report two methods to obtain interleukin (IL)-15-activated NK cells for clinical use. STUDY DESIGN AND METHODS: IL-15-activated NK cell products were obtained after 1) enrichment from healthy haploidentical donors' peripheral blood mononuclear cells (PBMNCs) collected by nonmobilized apheresis by a two-step magnetic procedure, depletion of CD3+ cells followed by selection of CD56+ cells and ex vivo overnight stimulation with IL-15 (NKIL15); and 2) expansion using the K562-mb15-41BBL cell line (NKAE), from autologous PBMNCs from patients with multiple myeloma or expansion from healthy haploidentical PBMNCs obtained from whole blood using the same previous cell line...
March 14, 2018: Transfusion
Wen-Han Yu, Cormac Cosgrove, Christoph T Berger, Patrick C Cheney, Marina Krykbaeva, Arthur Y Kim, Lia Lewis-Ximenez, Georg M Lauer, Galit Alter
Background: Hepatitis B virus (HBV) affects up to 400 million people worldwide and accounts for approximately one million deaths per year from liver pathologies. Current treatment regimens are effective in suppressing viremia but usually have to be taken indefinitely, warranting research into new therapeutic approaches. Acute HBV infection in adults almost universally results in resolution of viremia, with the exception of immunocompromised persons, suggesting that the immune response can functionally cure or even eradicate HBV infection...
2018: Pathogens & Immunity
Anh Duc Truong, Cong Thanh Hoang, Yeojin Hong, Janggeun Lee, Kyungbaek Lee, Hyun S Lillehoj, Yeong Ho Hong
The data herein is related to the research article entitled "Functional analyses of the interaction of chicken interleukin 23 subunit p19 with IL-12 subunit p40 to form the IL-23 complex" [1] where we demonstrated that the chicken interleukin (IL)-23α, IL-12p40, and IL-23 complex regulates Th1, Th17, and Treg cytokine production through heterodimer receptors as well as a homodimer receptor consisting of IL-12Rβ1 and IL-23R, and activates the JAK/STAT signaling pathways. Here, we evaluated the effects of the recombinant chicken IL-23α, IL-12p40, and IL-23 complex protein on cell proliferation and nitric oxide (NO) production in chicken macrophage (HD11) and CU91 T cell lines...
February 2018: Data in Brief
Taigo Kato, Tatsuo Matsuda, Yuji Ikeda, Jae-Hyun Park, Matthias Leisegang, Sachiko Yoshimura, Tetsuro Hikichi, Makiko Harada, Makda Zewde, Sho Sato, Kosei Hasegawa, Kazuma Kiyotani, Yusuke Nakamura
Neoantigens are the main targets of tumor-specific T cells reactivated by immune checkpoint-blocking antibodies or when using tumor-infiltrating T cells for adoptive therapy. While cancers often accumulate hundreds of mutations and harbor several immunogenic neoantigens, the repertoire of mutation-specific T cells in patients might be restricted. To bypass suboptimal conditions, which impede the reactivation of existing T cells or the priming of neoantigen-specific T cells in a patient, we employ T cells of healthy donors with an overlapping HLA repertoire to target cancer neoantigens...
February 16, 2018: Oncotarget
S Y N Jamaludin, I Azimi, F M Davis, A A Peters, T J Gonda, E W Thompson, S J Roberts-Thomson, G R Monteith
CXC ligand (L)12 is a chemokine implicated in the migration, invasion and metastasis of cancer cells via interaction with its receptors CXC chemokine receptor (CXCR)4 and CXCR7. In the present study, CXCL12-mediated Ca2+ signalling was compared with two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which demonstrate distinct metastatic potential. CXCL12 treatment induced Ca2+ responses in the more metastatic MDA-MB-231 cells but not in the less metastatic MDA-MB-468 cells. Assessment of mRNA levels of CXCL12 receptors and their potential modulators in both cell lines revealed that CXCR4 and CXCR7 levels were increased in MDA-MB-231 cells compared with MDA-MB-468 cells...
April 2018: Oncology Letters
Maria Vono, Christiane Sigrid Eberhardt, Elodie Mohr, Floriane Auderset, Dennis Christensen, Mirco Schmolke, Rhea Coler, Andreas Meinke, Peter Andersen, Paul-Henri Lambert, Beatris Mastelic-Gavillet, Claire-Anne Siegrist
Neonates and infants are more vulnerable to infections and show reduced responses to vaccination. Consequently, repeated immunizations are required to induce protection and early life vaccines against major pathogens such as influenza are yet unavailable. Formulating antigens with potent adjuvants, including immunostimulators and delivery systems, is a demonstrated approach to enhance vaccine efficacy. Yet, adjuvants effective in adults may not meet the specific requirements for activating the early life immune system...
2018: Frontiers in Immunology
Emilia Vendelova, Diyaaeldin Ashour, Patrick Blank, Florian Erhard, Antoine-Emmanuel Saliba, Ulrich Kalinke, Manfred B Lutz
Dendritic cells (DCs) are key directors of tolerogenic and immunogenic immune responses. During the steady state, DCs maintain T cell tolerance to self-antigens by multiple mechanisms including inducing anergy, deletion, and Treg activity. All of these mechanisms help to prevent autoimmune diseases or other hyperreactivities. Different DC subsets contribute to pathogen recognition by expression of different subsets of pattern recognition receptors, including Toll-like receptors or C-type lectins. In addition to the triggering of immune responses in infected hosts, most pathogens have evolved mechanisms for evasion of targeted responses...
2018: Frontiers in Immunology
Girak Kim, Min Jeong Gu, Soo Ji Kim, Kwang Hyun Ko, Yoon-Chul Kye, Cheol Gyun Kim, Jae-Ho Cho, Woon-Kyu Lee, Ki-Duk Song, Hyuk Chu, Yeong-Min Park, Seung Hyun Han, Cheol-Heui Yun
γδ T cells, known to be an important source of innate IL-17 in mice, provide critical contributions to host immune responses. Development and function of γδ T cells are directed by networks of diverse transcription factors (TFs). Here, we examine the role of the zinc finger TFs, Kruppel-like factor 10 (KLF10), in the regulation of IL-17-committed CD27- γδ T (γδ27- -17) cells. We found selective augmentation of Vγ4+ γδ27- cells with higher IL-17 production in KLF10-deficient mice. Surprisingly, KLF10-deficient CD127hi Vγ4+ γδ27- -17 cells expressed higher levels of CD5 than their wild-type counterparts, with hyper-responsiveness to cytokine, but not T-cell receptor, stimuli...
2018: Frontiers in Immunology
Cheol-Jung Lee, Su-Jin Moon, Jeong-Hee Jeong, Sangbae Lee, Mee-Hyun Lee, Sun-Mi Yoo, Hye Suk Lee, Han Chang Kang, Joo Young Lee, Weon Sun Lee, Hee-Jin Lee, Eun-Kyung Kim, Joo-Yeon Jhun, Mi-La Cho, Jun-Ki Min, Yong-Yeon Cho
Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis...
March 14, 2018: Cell Death & Disease
Nia Emami-Shahri, Julie Foster, Roxana Kashani, Patrycja Gazinska, Celia Cook, Jane Sosabowski, John Maher, Sophie Papa
The unprecedented efficacy of chimeric antigen receptor (CAR) T-cell immunotherapy of CD19+ B-cell malignancy has established a new therapeutic pillar of hematology-oncology. Nonetheless, formidable challenges remain for the attainment of comparable success in patients with solid tumors. To accelerate progress and rapidly characterize emerging toxicities, systems that permit the repeated and non-invasive assessment of CAR T-cell bio-distribution would be invaluable. An ideal solution would entail the use of a non-immunogenic reporter that mediates specific uptake of an inexpensive, non-toxic and clinically established imaging tracer by CAR T cells...
March 14, 2018: Nature Communications
Joao Incio, Jennifer A Ligibel, Daniel T McManus, Priya Suboj, Keehoon Jung, Kosuke Kawaguchi, Matthias Pinter, Suboj Babykutty, Shan M Chin, Trupti D Vardam, Yuhui Huang, Nuh N Rahbari, Sylvie Roberge, Dannie Wang, Igor L Gomes-Santos, Stefan B Puchner, Christopher L Schlett, Udo Hoffmman, Marek Ancukiewicz, Sara M Tolaney, Ian E Krop, Dan G Duda, Yves Boucher, Dai Fukumura, Rakesh K Jain
Anti-vascular endothelial growth factor (VEGF) therapy has failed to improve survival in patients with breast cancer (BC). Potential mechanisms of resistance to anti-VEGF therapy include the up-regulation of alternative angiogenic and proinflammatory factors. Obesity is associated with hypoxic adipose tissues, including those in the breast, resulting in increased production of some of the aforementioned factors. Hence, we hypothesized that obesity could contribute to anti-VEGF therapy's lack of efficacy. We found that BC patients with obesity harbored increased systemic concentrations of interleukin-6 (IL-6) and/or fibroblast growth factor 2 (FGF-2), and their tumor vasculature was less sensitive to anti-VEGF treatment...
March 14, 2018: Science Translational Medicine
Liam V Brown, Eamonn A Gaffney, Jonathan Wagg, Mark C Coles
Tumour immunotherapy is dependent upon activation and expansion of tumour-targetting immune cells, known as cytotoxic T-lymphocytes (CTLs). Cancer vaccines developed in the past have had limited success and the mechanisms resulting in failure are not well characterized. To elucidate these mechanisms, we developed a human-parametrized, in silico , agent-based model of vaccination-driven CTL activation within a clinical short-peptide vaccination context. The simulations predict a sharp transition in the probability of CTL activation, which occurs with variation in the separation rate (or off-rate) of tumour-specific immune response-inducing peptides (cognate antigen) from the major histocompatibility class I (MHC-I) receptors of dendritic cells (DCs) originally at the vaccination site...
March 2018: Journal of the Royal Society, Interface
Lisa M Ebert, Wenbo Yu, Tessa Gargett, Michael P Brown
Chimeric antigen receptor (CAR)-T cell therapy has been clinically validated as a curative treatment for the difficult to treat malignancies of relapsed/refractory B-cell acute lymphoblastic leukaemia and lymphoma. Here, the CAR-T cells are re-directed towards a single antigen, CD19, which is recognised as a virtually ideal CAR target antigen because it has strong, uniform expression on cancer cells, and is otherwise expressed only on healthy B cells, which are 'dispensable'. Notwithstanding the clinical success of CD19-CAR-T cell therapy, its single specificity has driven therapeutic resistance in 30% or more of cases with CD19-negative leukaemic relapses...
March 14, 2018: Biochemical Society Transactions
Mathew A Cherian, Sydney Olson, Hemalatha Sundaramoorthi, Kitra Cates, Xiaogang Cheng, John Harding, Andrew Martens, Grant A Challen, Manoj Tyagi, Lee Ratner, Daniel Rauch
The human T cell leukemia virus-1 (HTLV-1) oncoprotein Tax drives cell proliferation and resistance to apoptosis early in the pathogenesis of adult T-cell leukemia (ATL). Subsequently, likely as a result of specific immuno-editing, Tax expression is downregulated and functionally replaced by somatic driver mutations of the host genome. Both amplification and point mutations of interferon regulatory factor 4 (IRF4) have been previously detected in ATL, and the K59R mutation is the most common single-nucleotide variation in IRF4 and is found exclusively in ATL...
March 14, 2018: Journal of Biological Chemistry
Thenappan Thenappan, Mark L Ormiston, John J Ryan, Stephen L Archer
Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells...
March 14, 2018: BMJ: British Medical Journal
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