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Karina Trojan, Li Zhu, Mostafa Aly, Rolf Weimer, Nuray Bulut, Christian Morath, Gerhard Opelz, Volker Daniel
BACKGROUND: Little is known about a possible interaction of NK cells with Tregs in long-term stable kidney transplant recipients. METHODS: Absolute counts of lymphocyte and Treg subsets were studied in whole blood samples of 136 long-term stable renal transplant recipients and 52 healthy controls using eight-color-fluorescence flow cytometry. Patients were 1946±2201 days (153-10268 days) posttransplant and showed a serum creatinine of 1.7±0.7 mg/dl. RESULTS: Renal transplant recipients investigated >1...
February 14, 2017: Clinical and Experimental Immunology
Kankana Bardhan, Theodora Anagnostou, Vassiliki A Boussiotis
The immune system maintains a critically organized network to defend against foreign particles, while evading self-reactivity simultaneously. T lymphocytes function as effectors and play an important regulatory role to orchestrate the immune signals. Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. The immune system evolved various mechanisms to constrain such autoreactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (TRegs)...
2016: Frontiers in Immunology
Yanan Ding, Ranran Han, Wei Jiang, Jinting Xiao, Haijie Liu, Xiuju Chen, Xiaowen Li, Junwei Hao
Programmed death 1 (PD-1; CD279), a member of the CD28 family, is an inhibitory receptor on T cells and is responsible for T cell dysfunction in infectious diseases and cancers. The ligand for PD-1, programmed death ligand 1 (PD-L1; also known as B7-H1, CD274), is a member of the B7 family. The engagement of PD-1 with programmed death ligand can downregulate autoreactive T cells that participate in multiple autoimmune diseases. Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barré syndrome, and the pathogenesis of EAN is mediated principally through T cells and macrophages...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Anna Buermann, Dorothee Römermann, Wiebke Baars, Joachim Hundrieser, Jürgen Klempnauer, Reinhard Schwinzer
BACKGROUND: The development of donor-reactive antibodies is regarded to be an important barrier limiting long-term outcome of allo- and xenografts. We asked whether enhanced signaling via the co-inhibitory receptor programmed cell death-1 (PD-1; CD279) can downregulate human B-cell activation. METHODS: Proliferation of human purified CD19(+) B cells was induced by in vitro stimulation with CpG oligodeoxynucleotides (CpG-B). To induce antibody production, peripheral blood mononuclear cells were co-cultured with the porcine B-cell line L23...
September 2016: Xenotransplantation
Silvia Alberti-Violetti, Carlos A Torres-Cabala, Rakhshandra Talpur, Laura Corti, Daniele Fanoni, Luigia Venegoni, Emilio Berti, Madeleine Duvic
BACKGROUND: Primary cutaneous CD4+ small-/medium-sized pleomorphic T-cell lymphoma (CD4+ PCSM-TCL) is a rare lymphoproliferative disorder with a favorable prognosis. Distinguishing it from other cutaneous lymphomas is often a challenge. METHODS: We retrospectively collected CD4+PCSM-TCL cases from two centers (MD Anderson Cancer Center, USA and University of Milan, Italy) and evaluated their clinicopathological features. Array-comparative genomic hybridization (aCGH) analysis was performed on 11 cases...
December 2016: Journal of Cutaneous Pathology
Asif Sukri, Alfizah Hanafiah, Nik Ritza Kosai, Mustafa Mohamed Taher, Isa Mohamed Rose
BACKGROUND: Comprehensive immunophenotyping cluster of differentiation (CD) antigens in gastric adenocarcinoma, specifically between Helicobacter pylori-infected and -uninfected gastric cancer patients by using DotScan(™) antibody microarray has not been conducted. Current immunophenotyping techniques include flow cytometry and immunohistochemistry are limited to the use of few antibodies for parallel examination. We used DotScan(™) antibody microarray consisting 144 CD antibodies to determine the distribution of CD antigens in gastric adenocarcinoma cells and to elucidate the effect of H...
October 2016: Helicobacter
Guiyu Li, Caixia Lu, Jing Gao, Xietong Wang, Huanling Wu, Chao Lee, Baoxiang Xing, Qi Zhang
In this study, we try to testify the relationship between the programmed cell death receptor-1 (PD-1)/programmed cell death ligand 1 (PD-L1) passway and Treg cells in maternal-fetal immune regulation through PD-1 blockade on lymphocytes of normal early pregnancy in vitro and investigation of the PD-1 and PD-L1 changes in early recurrent miscarriage patients. CD4+ CD25+ Treg cells and PD-1 (CD279) positive cell were detected in deciduas in early recurrent miscarriage patients by flow cytometry. And the normal early pregnant women were as controls...
2015: International Journal of Clinical and Experimental Pathology
Jens Bedke, Stephan Kruck, Georgios Gakis, Arnulf Stenzl, Peter J Goebell
The introduction of targeted therapies like the tyrosine kinase (TKI) and mammalian target of rapamycin (mTOR) inhibitors has improved patients' survival in general. Nevertheless the prognosis remains limited. Therapies with a new mode of action are urgently warranted, especially those who would provoke long-term responders or long-lasting complete remissions as observed with unspecific immunotherapy with the cytokines interleukin-2 and interferon-α. In the recent years a deeper understanding of the underlying immunology of T cell activation led to the development of checkpoint inhibitors, which are mainly monocloncal antibodies and which enhances the presence of the co-stimulatory signals needed for T cell activation or priming...
2015: Human Vaccines & Immunotherapeutics
Marianne Boes, Friederike Meyer-Wentrup
Neuroblastoma is the most common extracranial solid tumor in children, causing 12% of all pediatric cancer mortality. Neuroblastoma specific T-cells have been detected in patients, but usually fail to attack and eradicate the tumors. Tumor immune evasion may thus play an important role in neuroblastoma pathogenicity. Recent research in adult cancer patients shows that targeting T-cell check-point molecules PD-1/PD-L1 (or CD279/CD274) may bolster immune reactivity against solid tumors. Also, infections can be associated with spontaneous neuroblastoma regression...
May 28, 2015: Cancer Letters
Lawrence Steinman
Immunologists are well aware that cancer regression and increased patient survival with the use of checkpoint inhibitors, such as ipilimumab, an antibody directed against cytotoxic T-lymphocyte-associated antigen 4, CTLA-4 (CD152), is accompanied by concomitant autoimmunity. For over 30 years, a small group of investigators have shown that the rare paraneoplastic syndromes are caused by immunity to shared antigens found on both tumors and on components of the nervous system. In this issue of the European Journal of Immunology, Blachère et al...
November 2014: European Journal of Immunology
Suzanne Ostrand-Rosenberg, Lucas A Horn, Samuel T Haile
Programmed death ligand 1 (PD-L1, also known as B7 homolog 1 or CD274) is a major obstacle to antitumor immunity because it tolerizes/anergizes tumor-reactive T cells by binding to its receptor programmed death-1 (CD279), renders tumor cells resistant to CD8(+) T cell- and FasL-mediated lysis, and tolerizes T cells by reverse signaling through T cell-expressed CD80. PD-L1 is abundant in the tumor microenvironment, where it is expressed by many malignant cells, as well as by immune cells and vascular endothelial cells...
October 15, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Josée Golay, Anna D'Amico, Gianmaria Borleri, Michela Bonzi, Rut Valgardsdottir, Rachele Alzani, Sabrina Cribioli, Clara Albanese, Enrico Pesenti, Maria Chiara Finazzi, Giulia Quaresmini, Dirk Nagorsen, Martino Introna, Alessandro Rambaldi
Current treatment of chronic lymphocytic leukemia (CLL) patients often results in life-threatening immunosuppression. Furthermore, CLL is still an incurable disease due to the persistence of residual leukemic cells. These patients may therefore benefit from immunotherapy approaches aimed at immunoreconstitution and/or the elimination of residual disease following chemotherapy. For these purposes, we designed a simple GMP-compliant protocol for ex vivo expansion of normal T cells from CLL patients' peripheral blood for adoptive therapy, using bispecific Ab blinatumomab (CD3 × CD19), acting both as T cell stimulator and CLL depletion agent, and human rIL-2...
November 1, 2014: Journal of Immunology: Official Journal of the American Association of Immunologists
Vassiliki A Boussiotis, Pranam Chatterjee, Lequn Li
Maintenance of peripheral tolerance is essential for homeostasis of the immune system. While central tolerance mechanisms result in deletion of the majority of self-reactive T cells, T lymphocytes specific for self-antigens also escape this process and circulate in the periphery. To control the development of autoimmunity, multiple mechanisms of peripheral tolerance have evolved, including T cell anergy, deletion, and suppression by regulatory T (Treg) cells. The pathway consisting of the programmed cell death 1 (PD-1) receptor (CD279) and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC; CD273) plays a vital role in the induction and maintenance of peripheral tolerance...
July 2014: Cancer Journal
Matthew J Ahearne, Kaljit Bhuller, Roger Hew, Hazem Ibrahim, Kikkeri Naresh, Simon D Wagner
The role of the microenvironment in high-grade lymphoma is not well defined. In this report, we employ immunohistochemistry to characterise programmed death-1 (PD-1/CD279) and FoxP3 expression in 70 cases of diffuse large B-cell lymphoma (DLBCL). PD-1 is a surface marker characteristic of follicular helper T-cells whilst FoxP3 is characteristic of Tregs. We demonstrate variable infiltration with CD4(+) T-cells (<10 to >50 % of all lymph node cells) and PD-1(hi) cells (0.1 to 1.5 % of all cells). CD4(+) T-cells can be distributed in clusters or more diffusely and PD-1(hi) cells, but not FoxP3(+) cells, are found in rosettes around lymphoma cells...
September 2014: Virchows Archiv: An International Journal of Pathology
Xiuxue Yu, Xueping Luo, Hongyan Xie, Dianhui Chen, Lu Li, Fan Wu, Changyou Wu, Anping Peng, Jun Huang
Gamma delta (γδ) T cells are mainly present in mucosa-associated lymphoid tissues, which play an important role in mucosal immunity. In this study, C57BL/6 mice were infected by Schistosoma japonicum and lymphocytes were isolated from the mesenteric lymph node (MLN) to identify changes in the phenotype and function of γδ T cells using flow cytometry. Our results indicated that the absolute number of γδ T cells from the MLNs of infected mice was significantly higher compared with normal mice (P < 0...
September 2014: Parasitology Research
Christopher H Cogbill, Steven H Swerdlow, Sarah E Gibson
OBJECTIVES: CD279 expression is used to help identify angioimmunoblastic T-cell lymphoma (AITL) or other T-cell lymphomas of T-follicular helper (TFH) cell origin; however, its utility in assessing lymphoid infiltrates in the bone marrow (BM) is not well established. METHODS: Immunohistochemistry for CD279 was performed on normal staging BM and in BM with benign lymphoid aggregates (LAs), AITLs, and other T-cell lymphomas. RESULTS: Seven of 10 staging BMs demonstrated scattered, usually weakly CD279+ cells...
July 2014: American Journal of Clinical Pathology
Babak Moradi, Philipp Schnatzer, Sébastien Hagmann, Nils Rosshirt, Tobias Gotterbarm, Jan Philippe Kretzer, Marc Thomsen, Hanns-Martin Lorenz, Felix Zeifang, Theresa Tretter
INTRODUCTION: CD4⁺CD25⁺/highCD127low/⁻ regulatory T cells (Tregs) play a crucial role in maintaining peripheral tolerance. Data about the frequency of Tregs in rheumatoid arthritis (RA) are contradictory and based on the analysis of peripheral blood (PB) and synovial fluid (SF). Because Tregs exert their anti-inflammatory activity in a contact-dependent manner, the analysis of synovial membrane (SM) is crucial. Published reports regarding this matter are lacking, so we investigated the distribution and phenotype of Tregs in concurrent samples of SM, SF and PB of RA patients in comparison to those of osteoarthritis (OA) patients...
2014: Arthritis Research & Therapy
Alena Gros, Paul F Robbins, Xin Yao, Yong F Li, Simon Turcotte, Eric Tran, John R Wunderlich, Arnold Mixon, Shawn Farid, Mark E Dudley, Ken-Ichi Hanada, Jorge R Almeida, Sam Darko, Daniel C Douek, James C Yang, Steven A Rosenberg
Adoptive transfer of tumor-infiltrating lymphocytes (TILs) can mediate regression of metastatic melanoma; however, TILs are a heterogeneous population, and there are no effective markers to specifically identify and select the repertoire of tumor-reactive and mutation-specific CD8⁺ lymphocytes. The lack of biomarkers limits the ability to study these cells and develop strategies to enhance clinical efficacy and extend this therapy to other malignancies. Here, we evaluated unique phenotypic traits of CD8⁺ TILs and TCR β chain (TCRβ) clonotypic frequency in melanoma tumors to identify patient-specific repertoires of tumor-reactive CD8⁺ lymphocytes...
May 2014: Journal of Clinical Investigation
Avadhesh Kumar Singh, Poonam Gaur, Satya N Das
Natural killer T (NKT) cells are a unique subset of glycolipid-reactive T lymphocytes that share properties with natural killer (NK) cells. These lymphocytes can produce array of cytokines and chemokines that modulate the immune response, and play a pivotal role in cancer, autoimmunity, infection and inflammation. Owing to these properties, NKT cells have gained attentions for its potential use in antitumor immunotherapies. To date several NKT cell-based clinical trials have been performed in patients with cancer using its potent ligand α-galactosylceramide (α-GalCer)...
March 2014: Human Immunology
Anna Sophie Berghoff, Gerda Ricken, Georg Widhalm, Orsolya Rajky, Johannes A Hainfellner, Peter Birner, Markus Raderer, Matthias Preusser
BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a malignant brain tumor with limited treatment options and shows prominent infiltration by tumor infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). Programmed death 1 (PD1; CD279) and its ligand PD-L1 (B7H1, CD274) promote escape of tumor cells from immune surveillance in several tumor types, but no data are available on PCNSL. Agents inhibiting PD1 and PD-L1 are showing compelling antitumor activity in current clinical trials in solid and hematological cancers...
January 2014: Clinical Neuropathology
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