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Christina M Mariaselvam, Ryad Tamouza, Rajagopal Krishnamoorthy, Dominique Charron, Durga Prasanna Misra, Vikramraj K Jain, Vir Singh Negi
INTRODUCTION: NKG2D (KLRK1) is a C-type lectin receptor present on NK cells, γδ, CD8(+) and CD4(+) T cells. Upon ligand binding, NKG2D mediates activatory and co-stimulatory signals to NK cells and activated CD4+ T cells, respectively. Polymorphisms in NKG2D predispose to infectious diseases, cancer, transplantation and autoimmune disorders. We studied the influence of this NK receptor polymorphism on predisposition to and modification of the disease phenotype in patients with Rheumatoid Arthritis (RA)...
October 26, 2016: Clinical and Experimental Immunology
Miljana Radenkovic, Kristina Uvebrant, Oskar Skog, Luis Sarmiento, Jeanette Avartsson, Peter Storm, Petter Vickman, Per-Anders Bertilsson, Malin Fex, Olle Korsgren, Corrado M Cilio
The current view of type 1 diabetes (T1D) is that it is an immune-mediated disease where lymphocytes infiltrate the pancreatic islets, promote killing of beta cells and cause overt diabetes. Although tissue resident immune cells have been demonstrated in several organs, the composition of lymphocytes in human healthy pancreatic islets have been scarcely studied. Here we aimed to investigate the phenotype of immune cells associated to human islets of non-diabetic organ donors. A flow cytometry analysis of isolated islets from perfused pancreases (n=38) was employed to identify alpha, beta, T, NK and B cells...
October 26, 2016: Clinical and Experimental Immunology
Clement Cochain, Alma Zernecke
Although infiltration of CD8(+) T cells in human atherosclerotic lesions has been described 30 years ago, the role of these cells in lesion development has long remained enigmatic. While experimental models hinted at their pro-atherogenic role based on circumstantial evidence, genetic mouse models of cytotoxic CD8(+) T cell-specific immune deficiency suggested no crucial role of these cells in lesion development. However, in recent years, more refined models of adoptive cell transfer, disruption of specific immune regulatory pathways or monoclonal antibody-mediated cell depletion have proposed both atheroprotective and pro-atherogenic functions for CD8(+) T cells in atherosclerosis...
November 2016: Basic Research in Cardiology
Sara De Biasi, Elena Bianchini, Milena Nasi, Margherita Digaetano, Lara Gibellini, Gianluca Carnevale, Vanni Borghi, Giovanni Guaraldi, Marcello Pinti, Cristina Mussini, Andrea Cossarizza
INTRODUCTION: Scanty data exist on the phenotype and functionality of invariant natural killer T (iNKT) cells in HIV-infected (HIV+) patients. METHODS: By flow cytometry, we studied iNKT cells from 54 HIV+ patients who started combined antiretroviral therapy and had undetectable viral load for more than 1 year. Twenty-five maintained a CD4/CD8 ratio less than 0.4, whereas 29 reached a ratio more than 1.1; 32 age-matched and sex-matched patients were healthy controls (CTR)...
November 13, 2016: AIDS
María de Lourdes Mora-García, Rosario García-Rocha, Omar Morales-Ramírez, Juan José Montesinos, Benny Weiss-Steider, Jorge Hernández-Montes, Luis Roberto Ávila-Ibarra, Christian Azucena Don-López, Marco Antonio Velasco-Velázquez, Vianey Gutiérrez-Serrano, Alberto Monroy-García
BACKGROUND: In recent years, immunomodulatory mechanisms of mesenchymal stem/stromal cells (MSCs) from bone marrow and other "classic" sources have been described. However, the phenotypic and functional properties of tumor MSCs are poorly understood. The aim of this study was to analyze the immunosuppressive capacity of cervical cancer-derived MSCs (CeCa-MSCs) on effector T lymphocytes through the purinergic pathway. METHODS: We determined the expression and functional activity of the membrane-associated ectonucleotidases CD39 and CD73 on CeCa-MSCs and normal cervical tissue-derived MSCs (NCx-MSCs)...
October 26, 2016: Journal of Translational Medicine
João Luiz Silva-Filho, Celso Caruso-Neves, Ana Acacia Sá Pinheiro
Angiotensin II (Ang II) and its receptor AT1 (AT1R), an important effector axis of renin-angiotensin system (RAS), have been demonstrated to regulate T-cell responses. However, these studies characterized Ang II and AT1R effects using pharmacological tools, which do not target only Ang II/AT1R axis. The specific role of AT1R expressed by antigen-specific CD8(+) T cells is unknown. Then we immunized transgenic mice expressing a T-cell receptor specific for SIINFEKL epitope (OT-I mice) with sporozoites of the rodent malaria parasite Plasmodium berghei expressing the cytotoxic epitope SIINFEKL...
October 26, 2016: Scientific Reports
Angelika Drynda, Bożena Obmińska-Mrukowicz, Ewa Zaczyńska, Michał Zimecki, Stanisław Ryng, Marcin Mączyński
OBJECTIVES: Immunoregulatory properties of 06K derivative (4-(4-chlorophenyl)-1-(5-amino-3-methylisoxazole-4-carbonyl)-thiosemicarbazide) in mouse in vivo models were investigated. METHODS: Several in vivo models were used: humoral and cellular immune response, carrageenan inflammatory reaction and determination of lymphocyte subsets in non-immunized mice. KEY FINDINGS: The compound administered before or after immunization with sheep erythrocytes (sheep red blood cell (SRBC)) elevated the number of plaque-forming cells (PFC), and this effect was stronger at lower doses...
October 26, 2016: Journal of Pharmacy and Pharmacology
C A Pope, Aruni Bhatnagar, James McCracken, Wesley T Abplanalp, Daniel J Conklin, Timothy E O'Toole
RATIONALE: Epidemiologic evidence indicates that exposures to fine particulate matter air pollution (PM2.5) contribute to global burden of disease, primarily as a result of increased risk of cardiovascular morbidity and mortality. However, mechanisms by which PM2.5 exposure induces cardiovascular injury remain unclear. PM2.5-induced endothelial dysfunction and systemic inflammation have been implicated, but direct evidence is lacking. OBJECTIVE: To examine whether acute exposure to PM2...
October 25, 2016: Circulation Research
Marina C Pils, Karla Dreckmann, Katharina Jansson, Silke Glage, Nadine Held, Wiebke Sommer, Florian Länger, Murat Avsar, Gregor Warnecke, André Bleich
Porcine reproductive and respiratory syndrome virus (PRRSV) infection was diagnosed in 6 Göttingen minipigs (Sus scrofa domestica) with severe interstitial pneumonia. The virus was defined as a North American (NA) subtype virus, which is common in the commercial pig population and might be derived from a widely used attenuated live-virus vaccine in Europe. The ORF5 sequence of the isolated PRRSV was 98% identical to the vaccine virus. The affected pigs were part of a lung transplantation model and received tacrolimus and steroids as well as irradiation or CD8 antibody for immunosuppression...
2016: Comparative Medicine
E Ilett, T Kottke, J Thompson, K Rajani, S Zaidi, L Evgin, M Coffey, C Ralph, R Diaz, H Pandha, K Harrington, P Selby, R Bram, A Melcher, R Vile
The anti-tumor effects associated with oncolytic virus therapy are mediated significantly through immune-mediated mechanisms which depends both on the type of virus and the route of delivery. Here, we show that intra-tumoral (i.t.) oncolysis by Reovirus induced the priming of a CD8+, Th1-type anti-tumor response. In contrast, systemically delivered VSV expressing a cDNA library of melanoma antigens (VSV-ASMEL) promoted a potent anti-tumor CD4+ Th17 response. Therefore, we hypothesised that combining the Reovirus-induced CD8+ T cell response, with the VSV-ASMEL CD4+ Th17 helper response, would produce enhanced anti-tumor activity...
October 25, 2016: Gene Therapy
Isolde G Rojas, Maria L Spencer, Paulina A Zapata, Alejandra Martínez, Rosario Alarcón, Francisco J Marchesani, Mine Tezal
BACKGROUND: Differences in immune profile between actinic cheilitis (AC), a precursor of lip squamous cell carcinoma, and normal lip vermillion (NL) have not been elucidated. OBJECTIVES: To compare density, distribution, and ratios of CD8+ and FoxP3+ cells between AC and NL and assess their associations with clinicopathologic variables. METHODS: Samples of AC and NL obtained between 2001 and 2013 at the College of Dentistry of the University of Concepcion, Chile, were retrospectively analyzed for immunohistochemical detection of CD8+ and FoxP3+ cells...
October 25, 2016: International Journal of Dermatology
Lun Cai, Lei Yu, Sa Liu, Tongxun Li, Xiaoping Zhang, Wei Cui, Jie Du, Qinyi Zhang
Accumulating evidence shows that immune cells play an important role in carotid atherosclerotic plaque development. In this study, we assessed the association of 6 different natural killer T (NKT) cell subsets, based on CD57 and CD8 expression, with risk for development of carotid atherosclerotic plaque (CAP). Molecular expression by peripheral NKT cells was evaluated in 13 patients with high-risk CAP and control without carotid stenosis (n = 18). High-risk CAP patients, compared with healthy subjects, had less percentage of CD57+CD8- NKT cell subsets (8...
October 24, 2016: Inflammation
Jiangao Zhu, Huiyao Chen, Xiaopei Huang, Songfu Jiang, Yiping Yang
Viral hepatitis remains a global health challenge despite recent progress in the development of more effective therapies. Although virus-specific CD8(+) and CD4(+) T cell responses are essential for viral clearance, it remains largely unknown what regulates T cell-mediated viral clearance. Thus, a better understanding of the regulation of anti-viral T cell immunity would be critical for the design of more effective therapies for viral hepatitis. Using a model of adenovirus-induced hepatitis, here we showed that adenoviral infection induced recruitment of Ly6C(hi) monocytes to the liver in a CCR2-dependent manner...
October 20, 2016: JCI Insight
Rajarsi Mandal, Yasin Şenbabaoğlu, Alexis Desrichard, Jonathan J Havel, Martin G Dalin, Nadeem Riaz, Ken-Wing Lee, Ian Ganly, A Ari Hakimi, Timothy A Chan, Luc G T Morris
Recent clinical trials have demonstrated a clear survival advantage in advanced head and neck squamous cell carcinoma (HNSCC) patients treated with immune checkpoint blockade. These emerging results reveal that HNSCC is one of the most promising frontiers for immunotherapy research. However, further progress in head and neck immuno-oncology will require a detailed understanding of the immune infiltrative landscape found in these tumors. We leveraged transcriptome data from 280 tumors profiled by The Cancer Genome Atlas (TCGA) to comprehensively characterize the immune landscape of HNSCC in order to develop a rationale for immunotherapeutic strategies in HNSCC and guide clinical investigation...
October 20, 2016: JCI Insight
Aaron J Martin, Matthew Clark, Gregory Gojanovich, Fatima Manzoor, Keith Miller, Douglas E Kline, Y Maurice Morillon, Bo Wang, Roland Tisch
There continues to be a need for immunotherapies to treat type 1 diabetes in the clinic. We previously reported that nondepleting anti-CD4 and -CD8 Ab treatment effectively reverses diabetes in new-onset NOD mice. A key feature of the induction of remission is the egress of the majority of islet-resident T cells. How this occurs is undefined. Herein, the effects of coreceptor therapy on islet T cell retention were investigated. Bivalent Ab binding to CD4 and CD8 blocked TCR signaling and T cell cytokine production, while indirectly downregulating islet chemokine expression...
October 20, 2016: JCI Insight
Viriya Kaewkangsadan, Chandan Verma, Jennifer M Eremin, Gerard Cowley, Mohammed Ilyas, Oleg Eremin
The tumour microenvironment consists of malignant cells, stroma, and immune cells. Prominent tumour-infiltrating lymphocytes (TILs) in breast cancer are associated with a good prognosis and are predictors of a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC). The contribution of different T effector/regulatory cells and cytokines to tumour cell death with NAC requires further characterisation and was investigated in this study. Breast tumours from 33 women with large and locally advanced breast cancers undergoing NAC were immunohistochemically (intratumoural, stromal) assessed for T cell subsets and cytokine expression using labelled antibodies, employing established semiquantitative methods...
2016: Journal of Immunology Research
Carlos A Castaneda, Elizabeth Mittendorf, Sandro Casavilca, Yun Wu, Miluska Castillo, Patricia Arboleda, Teresa Nunez, Henry Guerra, Carlos Barrionuevo, Ketty Dolores-Cerna, Carolina Belmar-Lopez, Julio Abugattas, Gabriela Calderon, Miguel De La Cruz, Manuel Cotrina, Jorge Dunstan, Henry L Gomez, Tatiana Vidaurre
AIM: To determine influence of neoadjuvant-chemotherapy (NAC) over tumor-infiltrating-lymphocytes (TIL) in triple-negative-breast-cancer (TNBC). METHODS: TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays (TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples...
October 10, 2016: World Journal of Clinical Oncology
MacLean Hall, Hao Liu, Mokenge Malafa, Barbara Centeno, Pamela J Hodul, José Pimiento, Shari Pilon-Thomas, Amod A Sarnaik
BACKGROUND: We evaluated whether tumor infiltrating lymphocytes (TIL) could be expanded from surgically resected tumors from pancreatic cancer patients. METHODS: Tumors were resected from pancreatic cancer patients. Tumors were minced into fragments and cultured in media containing high dose interleukin-2 (IL-2) for up to 6 weeks. T cell phenotype, activation markers, and reactivity were measured. RESULTS: TIL expansion was measured in 19 patient samples...
2016: Journal for Immunotherapy of Cancer
Ioannis Politikos, Haesook Kim, Theodoros Karantanos, Julia Brown, Sean McDonough, Lequn Li, Corey Cutler, Joseph H Antin, Karen K Ballen, Jerome Ritz, Vassiliki A Boussiotis
Umbilical cord blood (UCB) is a valuable graft source for allogeneic hematopoietic stem cell transplantation (HSCT) in patients who lack adult donors. UCB transplantation (UCBT) in adults results in delayed immune reconstitution leading to high infection-related morbidity and mortality. Angiogenic factors and markers of endothelial dysfunction have biologic and prognostic significance in conventional HSCT, but their role in UCBT has not been investigated. Furthermore, the interplay between angiogenesis and immune reconstitution has not been studied...
October 21, 2016: Biology of Blood and Marrow Transplantation
Johan Mj Van den Bergh, Eva Lion, Viggo Fi Van Tendeloo, Evelien Ljm Smits
Interleukin (IL)-15 as a stand-alone therapy can activate the antitumor functions of immune effector cells resulting in significant tumor regression. Interestingly, combining IL-15 with the α-moiety of its receptor (IL-15Rα), also called IL-15 transpresentation, increases the in vivo half-life of IL-15 and enhances binding of IL-15 with cells expressing the IL-15Rβγ, such as NK cells and CD8(+) T cells. These features enlarge the signal transmission of IL-15, resulting in improved proliferation and antitumor activities of both NK cells and CD8(+) T cells, eventually leading to enhanced killing of tumor cells...
October 21, 2016: Pharmacology & Therapeutics
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