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Nicolas Gourdin, Marion Bossennec, Céline Rodriguez, Selena Vigano, Christelle Machon, Camilla Jandus, David Bauché, Julien Faget, Isabelle Durand, Nicolas Chopin, Olivier Tredan, Julien C Marie, Bertrand Dubois, Jérôme Guitton, Pedro Romero, Christophe Caux, Christine Ménétrier-Caux
The production of CD73-derived Adenosine (Ado) by Tregs, has been proposed as a resistance mechanism to anti-PD1 therapy in murine tumor models. We reported that Human Tregs express the ecto-nucleotidase CD39, that generates AMP from ATP, but do not express the AMPase CD73. In contrast, CD73 defined a subset of effector CD4+ T cells (Teffs), enriched in polyfunctional Th1.17 cells characterized by expression of CXCR3, CCR6 and MDR1 and production of IL-17A/IFN-γ/IL-22/GM-CSF. CD39+ Tregs selectively targeted CD73+ Teffs through cooperative degradation of ATP into Ado inhibiting and restricting the ability of CD73+ Teffs to secrete IL-17A...
March 20, 2018: Cancer Research
Fang Xiao, Guo Ai, Weiming Yan, Xiaoyang Wan, Xiaoping Luo, Qin Ning
Autoimmune hepatitis (AIH) is a chronic autoimmune disease with the primary focus on autoreactive Th1-mediated response and cytotoxic T cells reaction. The contribution of natural killer cells (NK cells) to AIH remains poorly understood. In this project, we revealed that the frequency of peripheral NK cells, more accurately CD56dim NK subset, was reduced in AIH patients. The reduction of CD56dim NK was negatively correlated with disease progression. In experimental autoimmune hepatitis (EAH), hepatic accumulation of NK cells is observed along with a decrease of NK cells in the periphery...
December 21, 2017: Cellular Immunology
S N Yang, X Pu, S L Xiang, J P Chen, L Pei
Objective: To investigate the effect of brain derived neurotrophic factor (BDNF) on mesenchymal stem cells (MSC) inhibiting follicular helper T cells (Tfh cells). Methods: The contents of indoleamine 2,3-dioxygenase (IDO), IL-10, TGF-β and IL-21 in MSC culture supernatant were detected by ELISA; The peripheral blood of healthy volunteers were collected, and lymphocyte in peripheral blood was separated by human lymphocyte separation solution; Co-cultures of MSC and lymphocyte were performed by Transwell chamber, and the proportion of CD4(+)CXCR5(+) Tfh cells and their subtypes were detected by flow cytometry...
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
Katherine M Satrom, Kathleen Ennis, Brian M Sweis, Tatyana M Matveeva, Jun Chen, Leif Hanson, Akhil Maheshwari, Raghavendra Rao
BACKGROUND: Hyperglycemia is common in extremely low gestational age newborns (ELGAN) and is associated with increased mortality and morbidity, including abnormal neurodevelopment. Hippocampus-mediated cognitive deficits are common in this population, but the specific effects of hyperglycemia on the developing hippocampus are not known. METHODS: The objective of this study was to determine the acute and long-term effects of hyperglycemia on the developing hippocampus in neonatal rats using a streptozotocin (STZ)-induced model of hyperglycemia...
March 15, 2018: Journal of Neuroinflammation
Yang Zhang, Linjuan Xu, Minggang Peng
Objective: To deeply verify the clinical significance of CXCR3 in prediction of cancer patients' prognosis. Data sources: We performed a meta-analysis including 12 studies searched from PubMed, Web of Science, Embase, and Cochrane databases. A total of 1,751 patients were used to analyze the association between CXCR3 and patients' prognosis, based on either overall survival or time to tumor progression. Study selection: Studies evaluating CXCR3 expression for predicting prognosis in human solid tumors were included...
2018: OncoTargets and Therapy
Kostas Patas, Anne Willing, Cüneyt Demiralay, Jan Broder Engler, Andreea Lupu, Caren Ramien, Tobias Schäfer, Christian Gach, Laura Stumm, Kenneth Chan, Marissa Vignali, Petra C Arck, Manuel A Friese, Ole Pless, Klaus Wiedemann, Agorastos Agorastos, Stefan M Gold
While a link between inflammation and the development of neuropsychiatric disorders, including major depressive disorder (MDD) is supported by a growing body of evidence, little is known about the contribution of aberrant adaptive immunity in this context. Here, we conducted in-depth characterization of T cell phenotype and T cell receptor (TCR) repertoire in MDD. For this cross-sectional case-control study, we recruited antidepressant-free patients with MDD without any somatic or psychiatric comorbidities ( n  = 20), who were individually matched for sex, age, body mass index, and smoking status to a non-depressed control subject ( n  = 20)...
2018: Frontiers in Immunology
Matthew Wiest, Katherine Upchurch, Wenjie Yin, Jerome Ellis, Yaming Xue, Bobby Lanier, Mark Millard, HyeMee Joo, SangKon Oh
Background: T cells play a central role in chronic inflammation in asthma. However, the roles of individual subsets of T cells in the pathology of asthma in patients remain to be better understood. Methods: We investigated the potential signatures of T cell subset phenotypes in asthma using fresh whole blood from adult atopic asthma patients (n = 43) and non-asthmatic control subjects (n = 22). We further assessed their potential clinical implications by correlating asthma severity...
2018: Allergy, Asthma, and Clinical Immunology
Kyosuke Kanai, Ah-Mee Park, Akiko Watanabe, Tomohiro Arikawa, Teruhito Yasui, Hiroki Yoshida, Ikuo Tsunoda, Osamu Yoshie
IL-27 is an immunoregulatory cytokine consisting of p28 and EBI3. Its receptor also has two subunits, WSX1 and gp130. Although IL-27 promotes Th1 differentiation in naive T cells, it also induces IL-10 expression in effector Th1 cells to curtail excessive immune responses. By using p28-deficient mice and WSX1-deficient mice (collectively called IL-27-deficient mice), we examined the role of IL-27 in primary infection by murine γ-herpesvirus 68 (MHV68), a murine model of EBV. Upon airway infection with MHV68, IL-27-deficient mice had more aggravated lung inflammation than wild-type mice, although MHV68 infection per se was better controlled in IL-27-deficient mice...
March 2, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Maliha A Alikhan, Megan Huynh, A Richard Kitching, Joshua D Ooi
The kidney is vulnerable to injury, both acute and chronic from a variety of immune and metabolic insults, all of which at least to some degree involve inflammation. Regulatory T cells modulate systemic autoimmune and allogenic responses in glomerulonephritis and transplantation. Intrarenal regulatory T cells (Tregs), including those recruited to the kidney, have suppressive effects on both adaptive and innate immune cells, and probably also intrinsic kidney cells. Evidence from autoimmune glomerulonephritis implicates antigen-specific Tregs in HLA-mediated dominant protection, while in several human renal diseases Tregs are abnormal in number or phenotype...
2018: Clinical & Translational Immunology
Yared Hailemichael, Amber Woods, Tihui Fu, Qiuming He, Michael C Nielsen, Farah Hasan, Jason Roszik, Zhilan Xiao, Christina Vianden, Hiep Khong, Manisha Singh, Meenu Sharma, Faisal Faak, Derek Moore, Zhimin Dai, Scott M Anthony, Kimberly S Schluns, Padmanee Sharma, Victor H Engelhard, Willem W Overwijk
Anticancer vaccination is a promising approach to increase the efficacy of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) checkpoint blockade therapies. However, the landmark FDA registration trial for anti-CTLA-4 therapy (ipilimumab) revealed a complete lack of benefit of adding vaccination with gp100 peptide formulated in incomplete Freund's adjuvant (IFA). Here, using a mouse model of melanoma, we found that gp100 vaccination induced gp100-specific effector T cells (Teffs), which dominantly forced trafficking of anti-CTLA-4-induced, non-gp100-specific Teffs away from the tumor, reducing tumor control...
February 26, 2018: Journal of Clinical Investigation
Simone A Joosten, Krista E van Meijgaarden, Sandra M Arend, Corine Prins, Fredrik Oftung, Gro Ellen Korsvold, Sandra V Kik, Rob Jw Arts, Reinout van Crevel, Mihai G Netea, Tom Hm Ottenhoff
The lack of defined correlates of protection hampers development of vaccines against tuberculosis (TB). In vitro mycobacterial outgrowth assays are thought to better capture the complexity of the human host/Mycobacterium tuberculosis (Mtb) interaction. We used a PBMC-based "mycobacterial-growth-inhibition-assay" (MGIA) to investigate the capacity to control outgrowth of Bacille Calmette-Guérin (BCG). Interestingly, strong control of BCG outgrowth was observed almost exclusively in individuals with recent exposure to Mtb, but not in (long-term) latent TB infection, and only modestly in BCG vaccinees...
February 20, 2018: Journal of Clinical Investigation
Riddhima Banga, Francesco A Procopio, Alessandra Ruggiero, Alessandra Noto, Khalid Ohmiti, Matthias Cavassini, Jean-Marc Corpataux, William A Paxton, Georgios Pollakis, Matthieu Perreau
We recently demonstrated that lymph nodes (LNs) PD-1+ /T follicular helper (Tfh) cells from antiretroviral therapy (ART)-treated HIV-infected individuals were enriched in cells containing replication competent virus. However, the distribution of cells containing inducible replication competent virus has been only partially elucidated in blood memory CD4 T-cell populations including the Tfh cell counterpart circulating in blood (cTfh). In this context, we have investigated the distribution of (1) total HIV-infected cells and (2) cells containing replication competent and infectious virus within various blood and LN memory CD4 T-cell populations of conventional antiretroviral therapy (cART)-treated HIV-infected individuals...
2018: Frontiers in Immunology
Lara A Aqrawi, Margarita Ivanchenko, Albin Björk, Jorge I Ramírez Sepúlveda, Juliana Imgenberg-Kreuz, Marika Kvarnström, Philipp Haselmayer, Janicke Liaaen Jensen, Gunnel Nordmark, Karine Chemin, Kathrine Skarstein, Marie Wahren-Herlenius
Genetic investigations of Sjögren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. CXCR5 is a chemokine receptor expressed on B and T cell subsets, and binds the chemotactic ligand CXCL13. We here aimed to link the genetic association with functional effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait loci analysis of the 11q23.3 locus was performed using B cell mRNA expression data from genotyped individuals. Lymphocyte surface markers were assessed by flow cytometry, and CXCL13 levels by a proximity extension assay...
February 17, 2018: Clinical and Experimental Immunology
Nathan Karin, Hila Razon
Chemokines are mostly known for their chemotactic properties, and less for their ability to direct the biological function of target cells, including T cells. The current review focuses on a key chemokine named CXCL10 and its role in directing the migratory propertied and biological function of CD4+ and CD8+ T cells in the context of cancer and inflammatory autoimmunity. CXCR3 is a chemokine receptor that is abundant on CD4+ T cells, CD8+ T cells and NK cells. It has three known ligands: CXCL9, CXCL10 and CXCL11...
February 12, 2018: Cytokine
Marios Koutsakos, Adam K Wheatley, Liyen Loh, E Bridie Clemens, Sneha Sant, Simone Nüssing, Annette Fox, Amy W Chung, Karen L Laurie, Aeron C Hurt, Steve Rockman, Martha Lappas, Thomas Loudovaris, Stuart I Mannering, Glen P Westall, Michael Elliot, Stuart G Tangye, Linda M Wakim, Stephen J Kent, Thi H O Nguyen, Katherine Kedzierska
Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (T FH ) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5 - CXCR3 + antibody-secreting B cell population, CD21 hi CD27 + memory B cells, and CD21 lo CD27 + B cells...
February 14, 2018: Science Translational Medicine
Jiacheng Xu, Teng Ma, Guorong Deng, Jiawei Zhuang, Cheng Li, Shaohu Wang, Chen Dai, Xiaobiao Zhou, Zhonggui Shan, Zhongquan Qi
The interaction of chemokine (C-X-C motif) ligand 10 (CXCL10) with its receptor (CXCR3) is a critical process in recruiting donor reactive T cells to a graft and alloantigen-specific memory T (Tm) cells exert a principal function in promoting graft dysfunction during accelerated cardiac rejection. However, whether CXCL10 chemokine exerts any effects on acute accelerated rejection mediated by CD8+ Tm cells in a re-transplant model has remained elusive. The present study established a cardiac transplant model by advanced microsurgery technology and improved organ storage...
February 2018: Experimental and Therapeutic Medicine
Delia Blaya, Beatriz Aguilar-Bravo, Fengjie Hao, Silvia Casacuberta-Serra, Mar Coll, Luis Perea, Júlia Vallverdú, Isabel Graupera, Elisa Pose, Laura Llovet, Jordi Barquinero, Francisco Javier Cubero, Juan Caballería, Pere Ginès, Pau Sancho-Bru
miR-155 is involved in immune and inflammatory diseases and is associated with liver fibrosis and steatohepatitis. However, the mechanisms involved in miR-155 regulation of liver injury are largely unknown. The role of miR-155 in acute liver injury was assessed in wild type (WT), miR-155-/- and miR-155-/- mice transplanted with WT bone marrow. Additionally, miR-155 expression was evaluated in liver tissue and peripheral blood mononuclear cells (PBMC) of patients with autoimmune hepatitis. Concanavalin A (ConA) but not acetaminophen (APAP) treatment increased the expression of miR-155 in liver tissue of WT mice...
February 8, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Soledad Urra, Martin C Fischer, José R Martínez, Loreto Véliz, Paulina Orellana, Antonieta Solar, Karen Bohmwald, Alexis Kalergis, Claudia Riedel, Alejandro H Corvalán, Juan C Roa, Rodrigo Fuentealba, C Joaquin Cáceres, Marcelo López-Lastra, Augusto León, Nicolás Droppelmann, Hernán E González
Papillary thyroid cancer (PTC) is the most prevalent endocrine neoplasia. The increased incidence of PTC in patients with thyroiditis and the frequent immune infiltrate found in PTC suggest that inflammation might be a risk factor for PTC development. The CXCR3-ligand system is involved in thyroid inflammation and CXCR3 has been found upregulated in many tumors, suggesting its pro-tumorigenic role under the inflammatory microenvironment. CXCR3 ligands (CXCL4, CXCL9, CXCL10 and CXCL11) trigger antagonistic responses partly due to the presence of two splice variants, CXCR3A and CXCR3B...
January 5, 2018: Oncotarget
Jorrit De Waele, Elly Marcq, Jonas Rm Van Audenaerde, Jinthe Van Loenhout, Christophe Deben, Karen Zwaenepoel, Erik Van de Kelft, David Van der Planken, Tomas Menovsky, Johan Mj Van den Bergh, Yannick Willemen, Patrick Pauwels, Zwi N Berneman, Filip Lardon, Marc Peeters, An Wouters, Evelien Lj Smits
Prognosis of glioblastoma remains dismal, underscoring the need for novel therapies. Immunotherapy is generating promising results, but requires combination strategies to unlock its full potential. We investigated the immunomodulatory capacities of poly(I:C) on primary human glioblastoma cells and its combinatorial potential with programmed death ligand (PD-L) blockade. In our experiments, poly(I:C) stimulated expression of both PD-L1 and PD-L2 on glioblastoma cells, and a pro-inflammatory secretome, including type I interferons (IFN) and chemokines CXCL9, CXCL10, CCL4 and CCL5...
2018: Oncoimmunology
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