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Su Huang, Yingjia Shen, Duy Pham, Li Jiang, Zheng Wang, Mark H Kaplan, Guangjun Zhang, Jie Sun
IFN regulatory factor 4 (IRF4) is a key transcription factor that promotes effector CD8+ T cell differentiation and expansion. The roles of IRF4 in regulating the CD8+ T cell response to cytokines have not been explored. In this article, we show that IL-2 and IL-15 signaling and STAT5 activation regulate IRF4 expression in CD8+ T cells. Gene-expression profile analysis has also revealed that IRF4 is required for expression of the receptors of IL-2 family cytokines CD122 and CD127. We found that IRF4 binds directly to CD122 and CD127 gene loci, indicating that it may directly promote CD122 and CD127 gene transcription...
August 1, 2017: ImmunoHorizons
Mads N Olesen, Josefine R Christiansen, Steen Vang Petersen, Poul Henning Jensen, Wojciech Paslawski, Marina Romero-Ramos, Vanesa Sanchez-Guajardo
We have previously shown that immunological processes in the brain during α-synuclein-induced neurodegeneration vary depending on the presence or absence of cell death. This suggests that the immune system is able to react differently to the different stages of α-synuclein pathology. However, it was unclear whether these immune changes were governed by brain processes or by a direct immune response to α-synuclein modifications. We have herein locally increased the peripheral concentration of α-synuclein or its pathology-associated variants, nitrated or fibrillar, to characterize the modulation of the CD4 T cell pool by α-synuclein and brain microglia in the absence of any α-synuclein brain pathology...
January 2018: Heliyon
Zheyi Li, Ronald J Jackson, Charani Ranasinghe
This study demonstrates that the fate of a vaccine is influenced by the cytokines produced by the innate lymphoid cells (ILC) recruited to the vaccination site, and it is vaccine route and adjuvant dependent. Intranasal virus vaccination induced ST2/IL-33R+ ILC2 in lung, while intramuscular vaccination induced exclusively IL-25R+ ILC2 in muscle. Interestingly, a larger proportion of IL-13+ ILC2s were detected in muscle following i.m. viral vector vaccination compared to lung post i.n. delivery. These observations revealed that ILC2 were the main source of IL-13 at the vaccination site (24 h post vaccination) responsible for inducing T cells of varying avidities...
2018: NPJ Vaccines
Karolina Gołąb, Randall Grose, Veronica Placencia, Amittha Wickrema, Julia Solomina, Martin Tibudan, Evelyn Konsur, Kamil Ciepły, Natalia Marek-Trzonkowska, Piotr Trzonkowski, J Michael Millis, John Fung, Piotr Witkowski
The first clinical trials with adoptive Treg therapy have shown safety and potential efficacy. Feasibility of such therapy could be improved if cells are cryopreserved and stored until optimal timing for infusion. Herein, we report the evaluation of two cell-banking strategies for Treg therapy: 1) cryopreservation of CD4+ cells for subsequent Treg isolation/expansion and 2) cryopreservation of ex-vivo expanded Tregs (CD4+ CD25hi CD127lo/- cells). First, we checked how cryopreservation affects cell viability and Treg markers expression...
February 9, 2018: Oncotarget
Na Li, Vincent van Unen, Thomas Höllt, Allan Thompson, Jeroen van Bergen, Nicola Pezzotti, Elmar Eisemann, Anna Vilanova, Susana M Chuva de Sousa Lopes, Boudewijn P F Lelieveldt, Frits Koning
Innate lymphoid cells (ILCs) are abundant in mucosal tissues and involved in tissue homeostasis and barrier function. Although several ILC subsets have been identified, it is unknown if additional heterogeneity exists, and their differentiation pathways remain largely unclear. We applied mass cytometry to analyze ILCs in the human fetal intestine and distinguished 34 distinct clusters through a t-SNE-based analysis. A lineage (Lin)- CD7+ CD127- CD45RO+ CD56+ population clustered between the CD127+ ILC and natural killer (NK) cell subsets, and expressed diverse levels of Eomes, T-bet, GATA3, and RORγt...
March 6, 2018: Journal of Experimental Medicine
Artur Juszkiewicz, Piotr Basta, Elżbieta Petriczko, Bogusław Machaliński, Jerzy Trzeciak, Karolina Łuczkowska, Anna Skarpańska-Stejnborn
Background: The aim of this study was to analyze the response of selected components of the immune system in rowers to maximal physical exercise, and to verify if this response can be modulated by supplementation with spirulina (cyanobacterium Spirulina platensis ) . Method: The double-blind study included 19 members of the Polish Rowing Team. The subjects were randomly assigned to the supplemented group ( n  = 10), receiving 1500 mg of spirulina extract for 6 weeks, or to the placebo group ( n  = 9)...
2018: Journal of the International Society of Sports Nutrition
Yi Xu, Roberto Romero, Derek Miller, Pablo Silva, Bogdan Panaitescu, Kevin R Theis, Afrah Arif, Sonia S Hassan, Nardhy Gomez-Lopez
PROBLEM: Pathological inflammation is causally linked to preterm labor and birth, the leading cause of neonatal morbidity and mortality worldwide. Our aims were to investigate whether (i) the newly described family of innate lymphoid cells (ILCs) was present at the human maternal-fetal interface and (ii) ILC inflammatory subsets were associated with the pathological process of preterm labor. METHODS OF STUDY: Decidual leukocytes were isolated from women with preterm or term labor as well as from gestational age-matched non-labor controls...
February 19, 2018: American Journal of Reproductive Immunology: AJRI
Ali Khalili, Soheil Ebrahimpour, Iradj Maleki, Saeid Abediankenari, Mousa Mohammadnia Afrouzi
BACKGROUND: Regulatory T (Treg) cell play a key role in autoimmune diseases. We evaluated the regulatory function and frequency of Treg cells and secreted IL-10, IL-35 concentration in Crohn's disease (CD). METHODS: Twenty-three patients with CD and 25 healthy controls (HC) were included in this study. We analysed the alteration of Tregs frequency using flow cytometry for CD4, CD25, CD127 and FoxP3 markers. Surface expression of CD4, CD25 and CD127 markers were used for isolation of a relatively pure Treg cells...
February 16, 2018: Romanian Journal of Internal Medicine, Revue Roumaine de Médecine Interne
Qing Miao, Yan Wang, Yong-Ge Liu, Yi-Xin Ren, Hui Guan, Zhen Li, Wei Xu, Li Xiang
Background: Group 2 innate lymphoid cells (ILC2s) are a newly identified cell population with the potent capability to produce Th2-type cytokines in a non-antigen specific manner. Previous study demonstrated that enhanced circulating ILC2s in cat-allergic patient after experimental allergen challenge, whereas the effects of natural allergen exposure on peripheral ILC2s are still unclear. We therefore examined the variations in circulating ILC2s among asthmatic patients sensitized to different allergens in- and outside- pollen season...
2018: Allergy, Asthma, and Clinical Immunology
Andreas T Björklund, Mattias Carlsten, Ebba Sohlberg, Lisa L Liu, Trevor Clancy, Mohsen Karimi, Sarah Cooley, Jeffrey S Miller, Monika Klimkowska, Marie Schaffer, Emma Watz, Kristina I Wikstrom, Pontus Blomberg, Bjorn E Wahlin, Marzia Palma, Lotta Hansson, Per Ljungman, Eva Hellström-Lindberg, Hans-Gustaf Ljunggren, Karl-Johan Malmberg
PURPOSE: To evaluate the safety, efficacy and immunobiological correlates of allogeneic NK cell-based therapy in primary chemotherapy-refractory or relapsed high-risk myelodysplastic syndrome (MDS), secondary AML (MDS/AML), and de novo AML patients. EXPERIMENTAL DESIGN: Sixteen patients received fludarabine/cyclophosphamide conditioning combined with total lymphoid irradiation followed by adoptive immunotherapy with IL-2-activated haploidentical NK cells. RESULTS: NK cell infusions were well tolerated with only transient adverse events observed in the 16 patients...
February 14, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Marina Passos Torrealba, Kelly Cristina Manfrere, Denis R Miyashiro, Josenilson F Lima, Luana de M Oliveira, Nátalli Z Pereira, Jade Cury-Martins, Juliana Pereira, Alberto J S Duarte, Maria N Sato, José A Sanches
Sézary syndrome (SS) is a leukemic variant of cutaneous T cell lymphoma (CTCL), and the neoplastic CD4+ T cells of SS patients undergo intense clonal proliferation. Although Sézary cells have been studied extensively, studies on adaptive immunity regarding CD8+T cells are scarce. This study aimed to investigate activation marker expression in CD8+ T cells according to the differentiation stages and IL-7/IL7Rα axis responses of patients with SS. Moreover, this study aimed to verify the soluble forms of CD38, sCD127 and IL-7 in serum...
January 9, 2018: Oncotarget
Mohamed Labib Salem, Mohamed R El-Shanshory, Said H Abdou, Mohamed S Attia, Shymaa M Sobhy, Mona F Zidan, Abdel-Aziz A Zidan
INTRODUCTION: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children. The precise mechanism behind the relapse in this disease is not clearly known. One possible mechanism could be the accumulation of immunosuppressive cells, including myeloid-derived suppressor cells (MDSCs) and T regulatory cells (Tregs) which we and others have reported to mediate suppression of anti-tumor immune responses. AIM: In this study, we aimed to analyze the numbers of these cells in a population of B-ALL pediatric patients...
February 1, 2018: Immunopharmacology and Immunotoxicology
James M Mathew, Jessica H Voss, Scott T McEwen, Iwona Konieczna, Arjun Chakraborty, Xuemei Huang, Jie He, Lorenzo Gallon, Richard S Kornbluth, Joseph R Leventhal
Donor-specific CD4 + CD127 - CD25 + FOXP3 + regulatory T cells (AgTregs) have the potential to induce clinical transplant tolerance; however, their expansion ex vivo remains challenging. We optimized a novel expansion protocol to stimulate donor-specific Tregs using soluble 4-trimer CD40 ligand (CD40L)-activated donor B cells that expressed mature antigen-presenting cell markers. This avoided the use of CD40L-expressing stimulator cells that might otherwise result in potential cellular contamination. Purified allogeneic "recipient" CD4 + CD25 + Tregs were stimulated on days 0 and 7 with expanded "donor" B cells in the presence of IL-2, TGFβ and sirolimus (SRL)...
January 18, 2018: Scientific Reports
Jonadab E Olguín, Itzel Medina-Andrade, Emmanuel Molina, Armando Vázquez, Thalia Pacheco-Fernández, Rafael Saavedra, Carlos Pérez-Plasencia, Yolanda I Chirino, Felipe Vaca-Paniagua, Luis E Arias-Romero, Emma B Gutierrez-Cirlos, Sonia A León-Cabrera, Miriam Rodriguez-Sosa, Luis I Terrazas
Colorectal cancer (CRC) is the second most commonly diagnosed cancer in women and the third in men in North America and Europe. CRC is associated with inflammatory responses in which intestinal pathology is caused by different cell populations including a T cell dysregulation that concludes in an imbalance between activated T (Tact) and regulatory T (Treg) cells. Treg cells are CD4+Foxp3+ cells that actively suppress pathological and physiological immune responses, contributing to the maintenance of immune homeostasis...
2018: Journal of Cancer
Aditi Narsale, Rosita Moya, Joanna Davida Davies
CD4+ T cells that co-express CD25 and CD127 (CD25+ CD127+ ) make up around 20% of all circulating CD4+ memory T cells in healthy people. The clinical significance of these cells is that in children with type 1 diabetes their relative frequency at diagnosis is significantly and directly correlated with rate of disease progression. The purpose of this study was to further characterize the CD25+ CD127hi cells. We show that they are a mix of Th1 and Th2 cells however, they have a significantly higher relative frequency of pre-committed and committed Th2 cells, and secrete significantly higher levels of Th2-type cytokines than CD25- memory T cells...
March 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Anne Willing, Jan Jäger, Stefanie Reinhardt, Nina Kursawe, Manuel A Friese
Multiple sclerosis (MS) is a T cell-driven inflammatory disease of the CNS. Research on T cell subsets involved in MS pathogenesis has mainly focused on classical CD4+ T cells, especially Th17 cells, as they produce the proinflammatory, MS-associated cytokine IL-17. However, the abundant unconventional mucosal-associated invariant T (MAIT) cells are also able to produce IL-17. MAIT cells are characterized by high CD161 expression and a semi-invariant Vα7.2 TCR, with which they recognize bacterial and yeast Ags derived from the riboflavin (vitamin B2) metabolism...
January 3, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Huanrong Hou, Yi Kang, Yanli Zeng, Yukui Li, Jia Shang
Interleukin (IL)-7 is a potent proliferation, activation, and survival cytokine for CD8+ T cells to improve viral and tumor specific CD8+ T cell responses. However, the role of IL-7 in regulation of dysfunctional hepatitis C virus (HCV)-specific CD8+ T cells was not fully elucidated. Thus, a total of 53 patients with chronic hepatitis C and 24 healthy individuals were enrolled in the current study. Serum IL-7 and its receptor α chain CD127 expression was measured. The modulatory function of IL-7 to CD8+ T cells was investigated in both direct and indirect contact co-culture with HCVcc-infected Huh7...
February 2018: Cytokine
Hannah C Jeffery, Patrick McDowell, Philipp Lutz, Rebecca E Wawman, Sheree Roberts, Chris Bagnall, Jane Birtwistle, David H Adams, Ye Htun Oo
INTRODUCTION: Innate lymphoid cells (ILC) have been implicated in the initiation of inflammation and fibrosis in mice. However, ILC have not been characterized in inflamed human liver tissue. METHODS: Human intrahepatic lymphocytes were isolated by mechanical digestion and phenotyped by flow cytometry. Conditioned medium from cultures of primary human biliary epithelial cells, stellate cells, fibroblasts and inflamed human liver tissue was used to model the effects of the inflammatory liver environment of ILC phenotype and function...
2017: PloS One
Bobby W S Li, Ralph Stadhouders, Marjolein J W de Bruijn, Melanie Lukkes, Dior M J M Beerens, Maarten D Brem, Alex KleinJan, Ingrid Bergen, Heleen Vroman, Mirjam Kool, Wilfred F J van IJcken, Tata Nageswara Rao, Hans Jörg Fehling, Rudi W Hendriks
Group 2 innate lymphoid cells (ILC2) are implicated in allergic asthma as an early innate source of the type 2 cytokines IL-5 and IL-13. However, their induction in house dust mite (HDM)-mediated airway inflammation additionally requires T cell activation. It is currently unknown whether phenotypic differences exist between ILC2s that are activated in a T cell-dependent or T cell-independent fashion. Here, we compared ILC2s in IL-33- and HDM-driven airway inflammation. Using flow cytometry, we found that surface expression levels of various markers frequently used to identify ILC2s were dependent on their mode of activation, highly variable over time, and differed between tissue compartments, including bronchoalveolar lavage (BAL) fluid, lung, draining lymph nodes, and spleen...
2017: Frontiers in Immunology
Priyanka Sathe, Swee Heng Milon Pang, Rebecca Delconte, Ngaire Elwood, Nicholas D Huntington
Understanding the pathways and regulation of human haematopoiesis, in particular, lymphopoiesis, is vital to manipulation of these processes for therapeutic purposes. However, although haematopoiesis has been extensively characterised in mice, translation of these findings to human biology remains rudimentary. Here, we describe the isolation of three progenitor subsets from human foetal bone marrow that represent differential stages of commitment to the natural killer (NK) cell lineage based on IL-15 responsiveness...
December 15, 2017: International Journal of Molecular Sciences
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