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Ruchi Srivastava, Arif A Khan, Sumit Garg, Sabrina A Syed, Julie N Furness, Hawa Vahed, Tiffany Pham, Howard T Yu, Anthony B Nesburn, Lbachir BenMohamed
Herpes simplex virus 1 (HSV-1) infection is widespread among humans. The HSV-1 virion protein 13/14 (VP13/14), also known as UL47, is a tegument antigen targeted by CD8(+) T cells from HSV-seropositive individuals. However, whether VP13/14-specific CD8(+) T cells play a role in the natural protection seen in asymptomatic (ASYMP) individuals (individuals who have never had a clinical herpetic disease) has not been elucidated. Using predictive computer-assisted algorithms, we identified 10 potential HLA-A*02:01-restricted CD8(+) T-cell epitopes from the 693-amino-acid sequence of the VP13/14 protein...
January 15, 2017: Journal of Virology
Paola Lasso, Jose Mateus, Paula Pavía, Fernando Rosas, Nubia Roa, M Carmen Thomas, Manuel C López, John M González, Concepción J Puerta, Adriana Cuéllar
In mammals, chronic diseases resulting from infectious agents have been associated with functional T cell response deficiency, a high frequency of terminally differentiated T cells, the presence of monofunctional Ag-specific T cells, and increased expression of inhibitory receptors. Similar to other chronic diseases, the progressive loss of certain functional activities during Trypanosoma cruzi infection might result in the inability to control replication of this parasite. To examine this hypothesis, we evaluated the differentiation and cell effector function of CD8(+) T cells and characterized the expression of inhibitory receptors and the presence of the parasite in the bloodstream of chagasic patients...
October 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Mamdooh Ghoneum, Nouran Felo, Sudhanshu Agrawal, Anshu Agrawal
Lactobacilli have been widely studied for their probiotic effects and have been reported to function as antiviral and anticancer agents. However, the underlying mechanisms via immune modulation are poorly understood. PFT is a freeze dried compound of Lactobacillus kefiri P-IF with a unique composition and functionality. In this study, we examined the potential stimulatory effects of two concentrations (50 µg and 100 µg/mL) of PFT on human monocyte-derived dendritic cell (DC) function in vitro. Results showed that PFT upregulated the expression of DC surface co-stimulatory and maturation markers CD80, CD86, and HLADR in a concentration dependent manner...
December 2015: International Journal of Immunopathology and Pharmacology
Jason B Kaplan, Marina Grischenko, Francis J Giles
BACKGROUND: Acute lymphoblastic leukemia (ALL) is a potentially fatal disease that involves clonal expansion of early lymphoid progenitor cells. Much of drug development for ALL treatment involves targeting antigens of the clonal cell surface. Blinatumomab belongs to an emerging class of anti-cancer therapeutics referred to as bispecific T-cell engaging antibodies. The Food and Drug Administration approved its use in relapsed or refractory adult Philadelphia chromosome-negative B-cell precursor ALL in December of 2014...
December 2015: Investigational New Drugs
Madhu P Menon, Alina Nicolae, Hillary Meeker, Mark Raffeld, Liqiang Xi, Armin G Jegalian, Douglas C Miller, Stefania Pittaluga, Elaine S Jaffe
Primary central nervous system (CNS) lymphomas are relatively rare with the most common subtype being diffuse large B-cell lymphoma. Primary CNS T-cell lymphomas (PCNSTL) account for <5% of CNS lymphomas. We report the clinical, morphologic, immunophenotypic, and molecular characteristics of 18 PCNSTLs. Fifteen cases were classified as peripheral T-cell lymphoma, not otherwise specified, 2 of which were of γδ T-cell derivation and 1 was TCR silent; there was 1 anaplastic large cell lymphoma, ALK-positive and 2 anaplastic large cell lymphoma, ALK-negative...
December 2015: American Journal of Surgical Pathology
Takeshi Nakahara, Junna Oba, Chie Shimomura, Makiko Kido-Nakahara, Masutaka Furue
Dendritic cells (DCs) have a critical effect on the outcome of adaptive immune responses against growing tumors. Tumor-infiltrating dendritic cells (TIDCs) play diverse roles in the regulation of tumor regression or growth, but the characteristics that distinguish those effects are obscure. In this study, we investigated the frequency, phenotype and function of TIDCs over time from early stages of melanoma growth in mice. Flow cytometric analysis revealed that the tumors were infiltrated by a significant population of CD11c+MHCII+ DCs, especially at an early stage of tumor growth...
September 15, 2015: Journal of Investigative Dermatology
E M Bijker, R Schats, L G Visser, R W Sauerwein, A Scholzen
Immunization of malaria-naïve volunteers under chemoprophylaxis with Plasmodium falciparum sporozoites (CPS) efficiently and reproducibly induces sterile protection and thus constitutes an excellent model to study protective immune responses against malaria. Here, we performed the first longitudinal assessment of lymphocyte activation and differentiation kinetics during sporozoite immunization in 15 volunteers by ex vivo lymphocyte flow cytometry analysis. Both CD4 and CD8 T cells as well as γδT cells, NK cells and CD3+ CD56+ cells showed increased activation and proliferation following immunization...
November 2015: Parasite Immunology
Annette Pachnio, Jianmin Zuo, Gordon B Ryan, Jusnara Begum, Paul A H Moss
CMV infection is a significant cause of morbidity and mortality in immunocompromised individuals, and the development of a vaccine is of high priority. Glycoprotein B (gB) is a leading vaccine candidate but the glycoprotein H (gH) pentameric complex is now recognized as the major target for neutralizing Abs. However, little is known about the T cell immune response against gH and glycoprotein L (gL) and this is likely to be an important attribute for vaccine immunogenicity. In this study, we examine and contrast the magnitude and phenotype of the T cell immune response against gB, gH, and gL within healthy donors...
October 15, 2015: Journal of Immunology: Official Journal of the American Association of Immunologists
Syeda S Hassan, Muhammad Akram, Elizabeth C King, Hazel M Dockrell, Jacqueline M Cliff
BACKGROUND: The PD-1 axis is a cell intrinsic immunoregulatory pathway that mediates T cell exhaustion in chronic infection particularly in some viral infections. We hypothesized that PD-1, PD-L1 and PD-L2 would be highly expressed in untreated tuberculosis patients compared to controls due to their chronic infection and would decrease with successful TB treatment. MATERIALS AND METHODS: Untreated tuberculosis patients (n = 26) were recruited at diagnosis and followed up during treatment...
2015: PloS One
Xiaochen Li, Quansheng Lyu, Rui Xia, Yanzheng Gu, Tengfei Gao, Peijuan Yu, Xueguang Zhang, Yibei Zhu
OBJECTIVE: To investigate whether interleukin 33 (IL-33) can enhance cytokine secretion and killing activity of peripheral blood mononuclear cells (PBMCs) in vitro. METHODS: PBMCs were harvested from healthy volunteers and stimulated with different combination of cytokines (CD3 mAb/CD28 mAb/IL-2, CD3 mAb/CD28 mAb/IL-2/IL-12, CD3 mAb/CD28 mAb/IL-2/IL-12/IL-33) in vitro. The cells of each group were collected after 72 hours. Total RNA were extracted and assayed by real-time quantitative PCR (qRT-PCR) for the levels of interferon γ (IFN-γ) and granzyme B...
September 2015: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Kohei Hosokawa, Pawel Muranski, Xingmin Feng, Keyvan Keyvanfar, Danielle M Townsley, Bogdan Dumitriu, Jichun Chen, Sachiko Kajigaya, James G Taylor, Christopher S Hourigan, A John Barrett, Neal S Young
Emerging evidence indicates that microRNA control and modulate immunity. MicroRNA have not been investigated in acquired aplastic anemia, a T-cell-mediated immune disease. Analysis of 84 microRNA expression levels in CD4(+) and CD8(+) T cells of patients with aplastic anemia revealed concurrent down-regulation of miR-126-3p, miR-145-5p, miR-223-3p, and miR-199a-5p (>3-fold change, P<0.05) in both T-cell populations, which were unique in aplastic anemia compared to other hematologic disorders. MiR-126-3p and miR-223-3p were down-regulated in CD4(+) T effector memory cells, and miR-126-3p, miR-145-5p, and miR-223-3p were down-regulated in CD8(+) T effector memory and terminal effector cells...
December 2015: Haematologica
Ashish Kumar Singha, Bhaskar Bhattacharjee, Debasish Maiti
Chemotherapy for leukemia has severe toxicity and bone marrow transplantation is both financially and logistically demanding. Therefore, immunotherapy is a feasible and promising approach to treat leukemia. For immunotherapy, cytotoxic T lymphocytes (CTL) against leukemic cells were induced. In BALB/c mice, leukemia was induced by N-ethyl-N'-nitrosourea (ENU). The mice were treated with recombinant IL-3 and GM-CSF - both 5μg/kg/day for four days to induce functional CTL. The IL-3+GM-CSF treatment increased total leukocyte counts, accompanied by significant increase in CTL activity, in the leukemic mice...
August 24, 2015: Leukemia Research
Xiang Li, Weijing Yang, Yan Zou, Fenghua Meng, Chao Deng, Zhiyuan Zhong
Protein drugs as one of the most potent biotherapeutics have a tremendous potential in cancer therapy. Their application is, nevertheless, restricted by absence of efficacious, biocompatible, and cancer-targeting nanosystems. In this paper, we report that 2-[3-[5-amino-1-carboxypentyl]-ureido]-pentanedioic acid (Acupa)-decorated pH-responsive chimaeric polymersomes (Acupa-CPs) efficiently deliver therapeutic proteins into prostate cancer cells. Acupa-CPs had a unimodal distribution with average sizes ranging from 157-175 nm depending on amounts of Acupa...
December 28, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Xiaodan Zheng, Jianlan Xie, Xiaoge Zhou
Epstein-Barr virus (EBV)-associated T-cell lymphoproliferative disease (LPD) is not uncommon in China, but gastrointestinal involvement is very rare. We report on an immunocompetent patient with EBV-associated T-cell LPD of the colon. The 26-year-old man was initially misdiagnosed with ulcerative colitis (UC). A colon biopsy revealed the presence of small to medium-sized lymphoid cells infiltrating the intestinal wall. The neoplastic cells expressed CD3, CD5, and granzyme B, not CD56. EBV-encoded small ribonucleic acid was detected in the tumor cells of the colon as well as the lymph node, and the T-cell receptor gene rearrangement result displayed δ gene monoclonal rearrangement...
2015: International Journal of Clinical and Experimental Pathology
Yohannes Haile, Katia Carmine-Simmen, Camille Olechowski, Bradley Kerr, R Chris Bleackley, Fabrizio Giuliani
BACKGROUND: Multiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system (CNS). It is widely accepted that inflammatory cells play major roles in the pathogenesis of MS, possibly through the use of serine protease granzyme B (GrB) secreted from the granules of cytotoxic T cells. We have previously identified GrB as a mediator of axonal injury and neuronal death. In this study, our goal was to evaluate the effect of GrB inhibition in the human system in vitro, and in vivo in EAE using the newly isolated GrB-inhibitor serpina3n...
2015: Journal of Neuroinflammation
Felipe Flores-Santibáñez, Dominique Fernández, Daniel Meza, Gabriela Tejón, Leonardo Vargas, Lorena Varela-Nallar, Sebastián Arredondo, Victoria Guixé, Mario Rosemblatt, María Rosa Bono, Daniela Sauma
The CD73 ectonucleotidase catalyses the hydrolysis of AMP to adenosine, an immunosuppressive molecule. Recent evidence has demonstrated that this ectonucleotidase is up-regulated in T helper type 17 cells when generated in the presence of transforming growth factor-β (TGF-β), and hence CD73 expression is related to the acquisition of immunosuppressive potential by these cells. TGF-β is also able to induce CD73 expression in CD8(+) T cells but the function of this ectonucleotidase in CD8(+) T cells is still unknown...
December 2015: Immunology
Jinyan Liu, Feng Li, Yu Ping, Liping Wang, Xinfeng Chen, Dan Wang, Ling Cao, Song Zhao, Bing Li, Pawel Kalinski, Stephen H Thorne, Bin Zhang, Yi Zhang
Esophageal squamous cell carcinoma (ESCC) is a very common malignant tumor with poor prognosis in China. Chemokines secreted by tumors are pivotal for the accumulation of CD8(+) T lymphocytes within malignant lesions in several types of cancers, but the exact mechanism underlying CD8(+) T lymphocyte homing is still unknown in ESCC. In this study, we revealed that, compared with marginal tissues, the expression of both chemokine (C-C motif) ligand 5 (CCL5) and (C-X-C motif) ligand 10 (CXCL10) was upregulated in ESCC tissues...
September 22, 2015: Oncotarget
P Talayero, E Mancebo, J Calvo-Pulido, S Rodríguez-Muñoz, I Bernardo, R Laguna-Goya, F L Cano-Romero, A García-Sesma, C Loinaz, C Jiménez, I Justo, E Paz-Artal
We examined intraepithelial lymphocytes (IELs) in 213 ileal biopsies from 16 bowel grafts and compared them with 32 biopsies from native intestines. During the first year posttransplantation, grafts exhibited low levels of IELs (percentage of CD103(+) cells) principally due to reduced CD3(+) CD8(+) cells, while CD103(+) CD3(-) cell numbers became significantly higher. Changes in IEL subsets did not correlate with histology results, isolated intestine, or multivisceral transplants, but CD3(-) IELs were significantly higher in patients receiving corticosteroids...
January 2016: American Journal of Transplantation
Katalin Kis-Toth, Denis Comte, Maria P Karampetsou, Vasileios C Kyttaris, Lakshmi Kannan, Cox Terhorst, George C Tsokos
OBJECTIVE: Engagement of signaling lymphocytic activation molecule family member 4 (SLAMF4; CD244, 2B4) by its ligand SLAMF2 (CD48) modulates the function and expansion of both natural killer cells and a subset of cytotoxic CD8+ T cells. Because the cytotoxicity of CD8+ T lymphocytes isolated from patients with systemic lupus erythematosus (SLE) is known to be impaired, the aim of this study was to assess whether the expression and function of the checkpoint regulator SLAMF4 are altered on CD8+ T cells from patients with SLE...
January 2016: Arthritis & Rheumatology
Ivan Ho Chan, Victoria Wu, Melissa Bilardello, Elliot Mar, Martin Oft, Peter Van Vlasselaer, John Brian Mumm
Interleukin-10 (IL-10) exerts both immunosuppressive and immunostimulatory effects. While the immunosuppressive effects are widely known, it has only been recently reported that pegylated recombinant human IL-10 (PEG-rHuIL-10) elicits potent interferon-γ (IFN-γ) and CD8 T-cell-dependent antitumor effects in murine tumor models. In this study, we show that PEG-rHuIL-10 exerts immune inhibitory effects on human peripheral blood mononuclear cell (PBMC) bulk cultures and stimulatory effects in CD8 T cells within the same culture...
December 2015: Journal of Interferon & Cytokine Research
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