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Xintao Hu, Antonio Valentin, Frances Dayton, Viraj Kulkarni, Candido Alicea, Margherita Rosati, Bhabadeb Chowdhury, Rajeev Gautam, Kate E Broderick, Niranjan Y Sardesai, Malcolm A Martin, James I Mullins, George N Pavlakis, Barbara K Felber
HIV sequence diversity and the propensity of eliciting immunodominant responses targeting variable regions of the HIV proteome are hurdles in the development of an effective AIDS vaccine. An HIV-derived conserved element (CE) p24(gag) plasmid DNA (pDNA) vaccine is able to redirect immunodominant responses to otherwise subdominant and often more vulnerable viral targets. By homology to the HIV immunogen, seven CE were identified in SIV p27(Gag) Analysis of 31 rhesus macaques vaccinated with full-length SIV gag pDNA showed inefficient induction (58% response rate) of cellular responses targeting these CE...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
T Nguyen, S Johnston, L Clarke, P Smith, D Staines, S Marshall-Gradisnik
Transient receptor potential melastatin subfamily 3 (TRPM3) ion channels play a role in calcium (Ca(2+) ) cell signalling. Reduced TRPM3 has been identified in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) patients. However, the significance of TRPM3 and association with intracellular Ca(2+) mobilisation has yet to be determined. Fifteen CFS/ME patients (mean age 48.82 ± 9.83 years) and 25 health controls (mean age 39.2 ± 12.12 years) were examined. Isolated NK cells were labelled with fluorescent antibodies to determine TRPM3, CD107a, and CD69 receptors on CD56(Dim) CD16(+) NK cells and CD56(Bright) CD16(Dim/-) NK cells...
October 11, 2016: Clinical and Experimental Immunology
Martin R Goodier, Chiara Lusa, Sam Sherratt, Ana Rodriguez-Galan, Ron Behrens, Eleanor M Riley
Cross-linking of FcγRIII (CD16) by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells, contributing to control of intracellular pathogens; this pathway can also be targeted for immunotherapy of cancerous or otherwise diseased cells. However, downregulation of CD16 expression on activated NK cells may limit or regulate this response. Here, we report sustained downregulation of CD16 expression on NK cells in vivo after intramuscular (but not intranasal) influenza vaccination...
2016: Frontiers in Immunology
Daria L Ivanova, Rida Fatima, Jason P Gigley
Conventional natural killer (cNK) cells, members of group 1 innate lymphoid cells, are a diverse cell subpopulation based on surface receptor expression, maturation, and functional potential. cNK cells are critical for early immunity to Toxoplasma gondii via IFNγ production. Acute cNK cell responses to infection with different strains of T. gondii have not yet been characterized in detail. Here, we comprehensively performed this analysis with Type I virulent RH, Type II avirulent ME49, and fully attenuated Type I cps1-1 strains...
2016: Frontiers in Immunology
Anne Mobergslien, Qian Peng, Vlada Vasovic, Mouldy Sioud
Therapeutic strategies aiming at mobilizing immune effector cells to kill tumor cells independent of tumor mutational load and MHC expression status are expected to benefit cancer patients. Recently, we engineered various peptide-Fc fusion proteins for directing Fcg receptor-bearing immune cells toward tumor cells. Here, we investigated the immunostimulatory and anti-tumor effects of one of the engineered Fc fusion proteins (WN-Fc). In contrast to the Fc control, soluble WN-Fc-1 fusion protein activated innate immune cells (e...
October 4, 2016: Oncotarget
Lauren P McLaughlin, Haili Lang, Elizabeth Williams, Kaylor E Wright, Allison Powell, Conrad R Cruz, Anamaris M Colberg-Poley, Cecilia Barese, Patrick J Hanley, Catherine M Bollard, Michael D Keller
BACKGROUND AIMS: Human parainfluenza virus-3 (HPIV) is a common cause of respiratory infection in immunocompromised patients and currently has no effective therapies. Virus-specific T-cell therapy has been successful for the treatment or prevention of viral infections in immunocompromised patients but requires determination of T-cell antigens on targeted viruses. METHODS: HPIV3-specific T cells were expanded from peripheral blood of healthy donors using a rapid generation protocol targeting four HPIV3 proteins...
September 27, 2016: Cytotherapy
Andriani C Patera, Anne M Drewry, Katherine Chang, Evan R Beiter, Dale Osborne, Richard S Hotchkiss
Sepsis is a heterogeneous syndrome comprising a highly diverse and dynamic mixture of hyperinflammatory and compensatory anti-inflammatory immune responses. This immune phenotypic diversity highlights the importance of proper patient selection for treatment with the immunomodulatory drugs that are entering clinical trials. To better understand the serial changes in immunity of critically ill patients and to evaluate the potential efficacy of blocking key inhibitory pathways in sepsis, we undertook a broad phenotypic and functional analysis of innate and acquired immunity in the same aliquot of blood from septic, critically ill nonseptic, and healthy donors...
September 26, 2016: Journal of Leukocyte Biology
Carlos Santos, Pedro Ferreirinha, Hugo Sousa, Joana Ribeiro, Margarida M S M Bastos, Tiago Neto, Paula A Oliveira, Rui Medeiros, Manuel Vilanova, Rui M Gil da Costa
Bracken is a fern with worldwide distribution. Exposure to bracken toxins such as ptaquiloside is hypothesized to increase the risk of papillomavirus-related cancers of the upper digestive tract. Ptaquiloside is thought to be an immunosupressor, thus allowing for the development of viral lesions. We have used a human papillomavirus type 16-transgenic (K14-HPV16) mouse model to study the effects of ptaquiloside on tumour-infiltrating CD8(+) T lymphocytes, which are critical players in anti-tumour immunity. HPV16(+/-) mice received ptaquiloside (0...
September 15, 2016: Food and Chemical Toxicology
C Mee Ling Munier, David van Bockel, Michelle Bailey, Susanna Ip, Yin Xu, Sheilajen Alcantara, Sue Min Liu, Gareth Denyer, Warren Kaplan, Kazuo Suzuki, Nathan Croft, Anthony Purcell, David Tscharke, David A Cooper, Stephen J Kent, John J Zaunders, Anthony D Kelleher
BACKGROUND: Smallpox was eradicated by a global program of inoculation with Vaccinia virus (VV). Robust VV-specific CD4 T-cell responses during primary infection are likely essential to controlling VV replication. Although there is increasing interest in cytolytic CD4 T-cells across many viral infections, the importance of these cells during acute VV infection is unclear. METHODS: We undertook a detailed functional and genetic characterization of CD4 T-cells during acute VV-infection of humans...
October 17, 2016: Vaccine
Rezwanul Wahid, Stephanie Fresnay, Myron M Levine, Marcelo B Sztein
The live oral typhoid vaccine Ty21a elicits predominantly CD8+, as well as CD4+ T cells mediated immune responses.Clinical field studies showed that Ty21a is moderately effective against S. Typhi and S. Paratyphi B, but not S. Paratyphi A infections. In this study we describe the in depth characterization of S. Typhi, S. Paratyphi A and S. Paratyphi B cross-reactive CD4+ T cell responses elicited following immunization with Ty21a.PBMC samples were collected from 16 healthy volunteers before and 42/84days after Ty21a immunization and stimulated ex-vivo with Salmonella-infected targets...
September 12, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Elena Albiero, Eliana Amati, Elke Baumeister, Hermann Einsele, Götz U Grigoleit, Francesco Rodeghiero
Characterization of human cytomegalovirus-specific T cells (CMV-T) is of critical importance for their potential use in adoptive immunotherapy after allogeneic hematopoietic stem cell transplantation. Background frequencies of CMV-T in peripheral blood mononuclear cells (PBMCs) of CMV-seropositive healthy subjects are usually very low, hence the requirement for prolonged culture time and multiple stimulations to expand them. The evaluation of the end-culture specificity and composition has sometimes been neglected or difficult to assess in these settings...
November 2016: Journal of Immunotherapy
Katarina M Mirjačić Martinović, Nada Lj Babović, Radan R Džodić, Vladimir B Jurišić, Aleksandra Z Ninković, Gordana M Konjević
Considering tumor-mediated suppression of natural killer (NK) cells, the aim of this study was to investigate the in-vitro effects of interleukin (IL)-2 and IL-12, as immunostimulatory cytokines, on the functional and receptor characteristics of NK cells and their subsets in healthy control (HC) and metastatic melanoma (MM) patients. Peripheral blood mononuclear cells of 27 HC and 35 MM patients were stimulated in vitro with IL-2, IL-12, and their combination for functional and phenotypic analysis. IL-2, IL-12, and primarily their combination, significantly induced NK cell activity, CD107a degranulation marker, and perforin expression in NK cells and their subsets in HC and MM patients...
September 10, 2016: Melanoma Research
Inês Laginha, Marcel A Kopp, Claudia Druschel, Klaus-Dieter Schaser, Benedikt Brommer, Rick C Hellmann, Ralf Watzlawick, Ramin-Raul Ossami-Saidi, Harald Prüss, Vieri Failli, Christian Meisel, Thomas Liebscher, Erik Prilipp, Andreas Niedeggen, Axel Ekkernkamp, Ulrike Grittner, Sophie K Piper, Ulrich Dirnagl, Monica Killig, Chiara Romagnani, Jan M Schwab
BACKGROUND: Natural killer (NK) cells comprise the main components of lymphocyte-mediated nonspecific immunity. Through their effector function they play a crucial role combating bacterial and viral challenges. They are also thought to be key contributors to the systemic spinal cord injury-induced immune-deficiency syndrome (SCI-IDS). SCI-IDS increases susceptibility to infection and extends to the post-acute and chronic phases after SCI. METHODS AND DESIGN: The prospective study of NK cell function after traumatic SCI was carried out in two centers in Berlin, Germany...
2016: BMC Neurology
Aziz Hichami, Akadiri Yessoufou, François Ghiringhelli, Françoise Salvadori, Kabirou Moutairou, Narcisse Zwetyenga, Naim Akhtar Khan
Regulatory T (Treg) cells are important to induce and maintain immunological self-tolerance. Although the progress accomplished in understanding the functional mechanism of Treg cells, intracellular molecules that control the mechanisms of their suppressive capacity are still on investigation. The present study showed that peroxisome proliferator-activated receptor-alpha deficiency impaired the suppressive activity of Treg cells on CD4(+)CD25(-) and CD8(+) T cell proliferation. In Treg cells, PPARα gene deletion also induced a decrease of migratory abilities, and downregulated the expression of chemokine receptors (CCR-4, CCR-8 and CXCR-4) and p27(KIP1) mRNA...
September 6, 2016: Biochimie
Alejandra Pera, Anusha Vasudev, Crystal Tan, Hassen Kared, Rafael Solana, Anis Larbi
CD4(+) T cells are essential for human CMV infection control. CMV-specific CD4(+) T cells possess antiviral functions and participate in anti-CMV humoral/cellular responses. In the elderly, CMV infection impairs immunity to other viruses and has been traditionally associated with T cell senescence; however, recent results suggest that, in younger people, CMV confers immune protection against other pathogens (heterologous immunity). To shed light on this controversy, we analyzed latent CMV infection effects on the quality of young individuals' immune response, specifically, the presence of polyfunctional T cells through an extensive phenotypic and functional characterization of the CD4(+) T cell subset...
August 26, 2016: Journal of Leukocyte Biology
Roni Engelstein, Sharon Merims, Galit Eisenberg, Jonathan Cohen, Stephen Frank, Tamar Hamburger, Shoshana Frankenburg, Ilan Ron, Ruth Isacson, Tal Grenader, Hanna Steinberg, Cyrille J Cohen, Tamar Peretz, Michal Lotem
CD8 lymphocytes are mandatory mediators of tumor regression. To enhance their specific antitumor activity, we aimed to improve a melanoma cell-based vaccine by transfecting it with 4-1BB ligand, a costimulatory and immune modulatory molecule. Thirty-four American Joint Committee on Cancer (AJCC) stage IIB-IV patients were vaccinated with a melanoma antigen-rich cell line engineered to express HLA-A2 and 4-1BBL (M20/A2/BBL). Twelve serially recruited patients were monitored for interferon γ expression and CD107a mobilization before and after vaccination...
October 2016: Journal of Immunotherapy
Tristan Legris, Christophe Picard, Dilyana Todorova, Luc Lyonnet, Cathy Laporte, Chloé Dumoulin, Corinne Nicolino-Brunet, Laurent Daniel, Anderson Loundou, Sophie Morange, Stanislas Bataille, Henri Vacher-Coponat, Valérie Moal, Yvon Berland, Francoise Dignat-George, Stéphane Burtey, Pascale Paul
Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation...
2016: Frontiers in Immunology
Nandini B Makwana, Bree Foley, Silvia Lee, Sonia Fernandez, Ashley B Irish, Patricia Price
Whilst it is established that CMV disease affects NK-cell profiles, the functional consequences of asymptomatic CMV replication are unclear. Here we characterise NK cells in clinically stable renal transplant recipients (RTRs; n = 48) >2 years after transplantation. RTRs and age-matched controls (n = 32) were stratified by their CMV serostatus and the presence of measurable CMV DNA. CMV antibody or CMV DNA influenced expression of NKG2C, LIR-1, NKp30, NKp46 and FcRγ, a signalling adaptor molecule, on CD56(dim) NK cells...
August 26, 2016: European Journal of Immunology
Ying Ma, Linfeng Cheng, Bin Yuan, Yusi Zhang, Chunmei Zhang, Yun Zhang, Kang Tang, Ran Zhuang, Lihua Chen, Kun Yang, Fanglin Zhang, Boquan Jin
Hantavirus infections cause severe emerging diseases in humans and are associated with high mortality rates; therefore, they have become a global public health concern. Our previous study showed that the CD8(+) T-cell epitope aa129-aa137 (FVVPILLKA, FA9) of the Hantaan virus (HTNV) nucleoprotein (NP), restricted by human leukocyte antigen (HLA)-A*02, induced specific CD8(+) T-cell responses that controlled HTNV infection in humans. However, the in vivo immunogenicity of peptide FA9 and the effect of FA9-specific CD8(+) T-cell immunity remain unclear...
2016: Frontiers in Immunology
J Zhang, Y N Wang, J S Wang, L Wu, N Wei, L Fu, Z Gao, J H Chen, R J Pei, Z Wang
OBJECTIVE: To investigate the significance of pedigree genetic screening and rapid immunological parameters in the diagnosis of primary hemophagocytic lymphohistiocytosis (HLH). METHODS: Four cases of primary HLH patients with PRF1, UNC13D and SH2D1A gene mutations were conducted pedigree investigation, including family genetic screening and detections of immunological parameters (NK cell activity, CD107a degranulation and expression of HLH related defective protein), to evaluate the significance of these different indicators in the diagnosis of primary HLH and explore their correlations...
July 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
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