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June Ho Shin, Mikel D Haggadone, John B Sunwoo
The Distal-less (Dlx) homeobox transcription factors (TFs) play a prominent role in regulating multiple facets of vertebrate biology. Though widely studied as mediators of tissue development, recent work has uncovered a role for this TF family in modulating the vertebrate hematopoietic compartment. Pertinent to our study, murine Dlx1-3 are expressed in an innate lymphocyte population known as natural killer (NK) cells, and they are implicated to assume a functional role in the NK cell maturation pathway. However, Dlx target genes are poorly understood...
September 2016: Biochemistry and Biophysics Reports
Honggeng Guan, Yuqiu Wan, Jing Lan, Qin Wang, Zhangyu Wang, Yecheng Li, Jiqing Zheng, Xueguang Zhang, Zemin Wang, Yueping Shen, Fang Xie
Regulatory T cells (Tregs), a key mediator in regulating anti-tumor immune suppression, tumor immune escape, metastasis and relapse, are considered an important therapeutic target in immunotherapy of human cancers. In the present investigation, elevated CD19(+) CD24(+) CD38(+) regulatory B cells (Bregs) were observed in PBMCs of invasive carcinoma of breast (IBCa) patients compared with that in patients with fibroadenoma (FIBma) or healthy individuals, and the positive correlation existed between Bregs and CD4(+) CD25(+) CD127(-) Tregs (r = 0...
October 20, 2016: Scientific Reports
Wenfang Xu, Jie Li, Yong Wu, Jiankang Zhou, Jianping Zhong, Qiuqiong Lv, Hui Shao, Heping Rao
OBJECTIVE: To evaluate cluster of differentiation (CD)127 expression in T cells of patients with HIV-1 and the relationship of CD127 expression with disease progression. METHODS: We divided 139 patients infected with human immunodeficiency virus type 1 (HIV-1) who had undergone highly active antiretroviral therapy (HAART) into 3 groups: patients with poor recovery (CD4(+)T < 350/µL, patients with general recovery (CD4(+)T =  350 - ∼600/µL) and patients with good recovery (CD4(+)T > 600/µL)...
October 19, 2016: Laboratory Medicine
Denise S M Medrado da Costa, Joana Hygino, Thais B Ferreira, Taissa M Kasahara, Priscila O Barros, Clarice Monteiro, Aleida Oliveira, Felipe Tavares, Claudia Cristina Vasconcelos, Regina Alvarenga, Cleonice A M Bento
Vitamin D deficiency is an environmental risk factor for MS, a Th17 cell-mediated autoimmune disease that results in demyelination in the CNS. Therefore, we aimed to evaluate the ability of in vitro 1,25(OH)2D in modulating different Th17 cell subsets in MS patients in remission phase. In the present study, the production of Th17-related cytokines (IL-1β, IL-6, IL-17, IL-22), as well as GM-CSF, was significantly higher in cell cultures from MS patients than in healthy subjects (HS). The 1,25(OH)2D reduced all pro-inflammatory cytokines essayed, mainly those released from HS cell cultures...
October 15, 2016: Journal of Neuroimmunology
Sanjay B Rathod, Anuradha S Tripathy
BACKGROUND AND AIM: Literature on the role of Regulatory T cells (Tregs) in acute viral infections is limited. Having established that the Tregs in self-limiting hepatitis E infection are elevated and functional, this study has focused on characterizing the specificity, phenotypes and identifying the molecules or factors responsible for enhancement of Treg cells and abrogation of Treg-mediated suppression in hepatitis E. METHODS: HEV rORF2p specific (a) Treg frequency, subset analysis and expression of surface and intracellular markers on Tregs and CFSE based functional analysis by flow cytometry (b) key cytokines quantification by multiplex (c) suppressive functional assay in the presence of anti-TGF-β1 or anti-IL-10 or both antibodies or Transwell insert or in combination were performed on samples from 58 acute patients (AVH-E), 45 recovered individuals from hepatitis E and 55 controls...
October 6, 2016: Human Immunology
Mary Prahl, Prasanna Jagannathan, Tara I McIntyre, Ann Auma, Lila Farrington, Samuel Wamala, Mayimuna Nalubega, Kenneth Musinguzi, Kate Naluwu, Esther Sikyoma, Rachel Budker, Hilary Vance, Pamela Odorizzi, Patience Nayebare, John Ategeka, Abel Kakuru, Diane V Havlir, Moses R Kamya, Grant Dorsey, Margaret E Feeney
BACKGROUND: In malaria-endemic areas, the first exposure to malaria antigens often occurs in utero when the fetal immune system is poised towards the development of tolerance. Children exposed to placental malaria have an increased risk of clinical malaria in the first few years of life compared to unexposed children. Recent work has suggested the potential of pregnancy-associated malaria to induce immune tolerance in children living in malaria-endemic areas. A study was completed to evaluate the effect of malaria exposure during pregnancy on fetal immune tolerance and effector responses...
October 7, 2016: Malaria Journal
Sarvari Velaga, Christina Alter, Ulrike Dringenberg, Christina T Thiesler, Sandra Kuhs, Sven Olek, Sya N Ukena, Anke Franzke
OBJECTIVE: Recent clinical trials have shown the high potential of regulatory T cells (Tregs) in prevention of acute and chronic graft-versus-host disease (GvHD) following hematopoietic stem cell transplantation but immune interventions require high Treg cell numbers. With respect to limited natural occurrence, development and optimization of large-scale expansion protocols of clinical-grade Tregs are essential if considered for therapeutic use. METHODS: We compared different clinical grade large-scale expansion protocols for repetitive transfer of high Treg cell numbers in clinical trials for the prevention of acute and/or chronic GvHD...
September 27, 2016: Experimental Hematology
Weiming Xiao, Min Yin, Keyan Wu, Guotao Lu, Bin Deng, Yu Zhang, Li Qian, Xiaoqing Jia, Yanbing Ding, Weijuan Gong
Wogonin exerts anti-tumour activities via multiple mechanisms. We have identified that high-dose wogonin (50 or 100 mg/kg) could inhibit the growth of transplanted tumours by directly inducing tumour apoptosis and promoting DC, T and NK cell recruitment into tumour tissues to enhance immune surveillance. However, wogonin (20-50 μM) ex vivo prevents inflammation by inhibiting NF-κB and Erk signalling of macrophages and epithelial cells. It is elusive whether high-dose wogonin promotes or prevents inflammation...
September 19, 2016: Journal of Cellular and Molecular Medicine
Ilona Kryczek, Lin Wang, Ke Wu, Wei Li, Ende Zhao, Tracy Cui, Shuang Wei, Yan Liu, Yin Wang, Linda Vatan, Wojciech Szeliga, Joel K Greenson, Jacek Roliński, Witold Zgodzinski, Emina Huang, Kaixiong Tao, Guobin Wang, Weiping Zou
Foxp3(+)CD4(+) regulatory T (Treg) cells are thought to express negligible levels of effector cytokines, and inhibit immune responses and inflammation. Here, we have identified a population of IL-8(+)Foxp3(+)CD4(+) T cells in human peripheral blood, which is selectively increased in the microenvironments of ulcerative colitis and colon carcinoma. Phenotypically, this population is minimally overlapping with IL-17(+)Foxp3(+)CD4(+) T cells, and is different from IL-8(-)Foxp3(+)CD4(+) T cells in the same microenvironment...
August 2016: Oncoimmunology
Morteza Jafarinia, Fereshteh Mehdipour, Seyed Vahid Hosseini, Leila Ghahramani, Masood Hosseinzadeh, Abbas Ghaderi
CD4(+)CD25(-)FoxP3(+) cells are a newly recognized subset of T cells which was first reported in autoimmune diseases. In our previous study, this subset was detected in tumor-draining lymph nodes (TDLNs) of patients with breast cancer. As little is known about their function in TDLNs of cancer patients, in this study, their frequency as well as their ability to produce interleukin (IL)-2, IL-10, or interferon (IFN)-γ were investigated in TDLNs of colorectal cancer (CRC) patients. Mononuclear cells were isolated from lymph nodes of 13 patients with CRC using Ficoll-Hypaque gradient centrifugation...
September 13, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Scott Sugden, Feras Ghazawi, Paul MacPherson
HIV-1 Tat protein down regulates expression of the IL-7 receptor alpha-chain (CD127) from the surface of CD8 T cells resulting in impaired T cell proliferation and cytolytic capacity. We have previously shown that soluble Tat protein is taken up by CD8 T cells and interacts with the cytoplasmic tail of CD127 to induce receptor degradation. The N-terminal domain of Tat interacts with CD127 while the basic domain directs CD127 to the proteasome. We have also shown that upon IL-7 binding to its receptor, CD127 is phosphorylated resulting in CIS-mediated proteasomal degradation...
November 2016: Virology
Jing Cheng, Yingying Chen, Banglong Xu, Jixiong Wu, Fei He
Objective The purpose of this study was to investigate the relationship between circulating soluble fibrinogen-like protein 2 (sFGL2) concentrations and the severity of coronary artery disease (CAD) in patients who underwent first-time angiography for suspected CAD. Methods Serum sFGL2 concentrations were measured in 102 consecutive patients by an enzyme-linked immunosorbent assay (ELISA). The number of circulating CD4(+)CD25(+)CD127(low) T regulatory cells (Tregs) was determined by flow cytometry and effecter cytokines, including transforming growth factor-β1 and interleukin-10 (IL-10), were also evaluated by an ELISA...
2016: Internal Medicine
Martha Zewdie, Rawleigh Howe, Søren T Hoff, T Mark Doherty, Nahom Getachew, Azeb Tarekegne, Bamlak Tessema, Lawrence Yamuah, Abraham Aseffa, Markos Abebe
BACKGROUND: Regulatory T cells (Treg) are an essential arm of adaptive immunity not only in tolerance and autoimmunity but also in infectious diseases. In Tuberculosis (TB), it has been suggested that the frequency of Tregs is higher in the blood of TB patients when compared to healthy controls with subsequent decline after treatment. However, with the discovery that FOXP3, the hallmark marker of Tregs, is not exclusive to Tregs and the lack of specific markers for Tregs, it has been a challenge to fully understand the role of Tregs in TB...
September 2016: Tuberculosis
Juzer A Kakal, Feras M Ghazawi, Elliott M Faller, Scott M Sugden, Parmvir Parmar, Paul A MacPherson
Interleukin-7 is essential for the development and maintenance of T cells, and the expression of the IL-7 receptor is tightly regulated at every stage of the T cell's lifespan. In mature CD8 T cells, IL-7 plays important roles in cell survival, peripheral homeostasis, and cytolytic function. The IL-7 receptor alpha-chain (CD127) is expressed at high levels on naïve and memory cells, but it is rapidly downregulated upon IL-7 stimulation. In this study, we illustrate the dynamicity of the CD127 promoter and show that it possesses positive as well as negative regulatory sites involved in upregulating and downregulating CD127 expression, respectively...
August 19, 2016: Immunogenetics
Suresh Gopi Kalathil, Amit Anand Lugade, Austin Miller, Renuka Iyer, Yasmin Thanavala
BACKGROUND: Sorafenib is an oral antiangiogenic agent administered in advanced-stage hepatocellular carcinoma (HCC). Based on preclinical and human studies, we hypothesized that, in addition to its antiangiogenic properties, sorafenib may beneficially reduce the extent of the immunosuppressive network in HCC patients. To test this hypothesis, we examined whether alterations in the immunosuppressive burden of advanced-stage HCC patients correlated with clinical outcome. METHODS: In before and after sorafenib treatment, blood samples collected from 19 patients with advanced HCC, the frequency of PD-1(+) T cells, Tregs, and myeloid derived suppressor cells (MDSC) were quantified by multiparameter FACS...
July 21, 2016: JCI Insight
Chie Sugimoto, Makoto Hirotani, Kazunori Yoshikiyo, Uichi Koshimizu, Rika Wakao, Takahiro Horinouchi, Yuichi Mazaki, Tsunehiko Higashi, Toshiyuki Fukazawa, Hiroyoshi Fujita, Hidenao Sasaki, Hiroshi Wakao
BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelination, gliosis and axonal loss in the Central Nervous System. Although the etiology of the disease has remained enigmatic, recent studies have suggested a role of the innate-like T cells, called Mucosal Associated Invariant T cells (MAITs) in the pathophysiology. In the present study, we have analyzed the relative frequency of MAITs and the expression of the cell surface antigens in MAITs to seek a possible link to the disease...
2016: SpringerPlus
P N Kravchenko, G A Zhulai, A V Churov, E K Oleinik, V M Oleinik, O Yu Barysheva, N N Vezikova, I M Marusenko
BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory rheumatic disease associated with a dysfunction of the T cell-mediated tolerance and leading to the disability of working population. The regulatory CD4' T cells play an important role in the regulation of autoimmunity and can suppress immune responses. With that, there is no consensus on the content of these lymphocytes and their role in the pathogenesis of RA. Objective: The aim of the study was to assess the content ofperipheral blood regulatory Tcells (Treg) according to the expression of membrane markers CD4, CD25, CD127 and intracellular FOXP3 marker, as well as the expression of two functional molecules (CTLA-4 and CCR4) in Treg cells of patients with RA...
2016: Vestnik Rossiĭskoĭ Akademii Meditsinskikh Nauk
Jessica K Fiege, Lalit K Beura, Brandon J Burbach, Yoji Shimizu
During acute infections, naive Ag-specific CD8 T cells are activated and differentiate into effector T cells, most of which undergo contraction after pathogen clearance. A small population of CD8 T cells persists as memory to protect against future infections. We investigated the role of adhesion- and degranulation-promoting adapter protein (ADAP) in promoting CD8 T cell responses to a systemic infection. Naive Ag-specific CD8 T cells lacking ADAP exhibited a modest expansion defect early after Listeria monocytogenes or vesicular stomatitis virus infection but comparable cytolytic function at the peak of response...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Konstantinos Samitas, Carina Malmhäll, Madeleine Rådinger, Patricia Ramos-Ramirez, You Lu, Tünde Deák, Maria Semitekolou, Mina Gaga, Margareta Sjöstrand, Jan Lötvall, Apostolos Bossios
BACKGROUND: B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive. METHODS: A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry...
2016: PloS One
Hans Jakob Hartling, Sofie Jespersen, Julie Christine Gaardbo, Camilla Sambleben, Kristina Thorsteinsson, Jan Gerstoft, Henrik Ullum, Susanne Dam Nielsen
BACKGROUND: Late presentation of HIV infection is associated with reduced chance of optimal immune recovery after initiating combination antiretroviral therapy (cART). Interleukin-7 (IL-7) and the corresponding receptor, IL-7 receptor (IL-7R) made up of CD127 and CD132, are crucial for T cell homeostasis. This study aimed to describe IL-7R and IL-7 before and after initiation of cART in late presenting HIV-infected individuals, and the impact on immune recovery and T cell subset distribution after initiation of cART...
August 5, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
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