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https://www.readbyqxmd.com/read/28239463/enhancing-adoptive-cancer-immunotherapy-with-v%C3%AE-2v%C3%AE-2-t-cells-through-pulse-zoledronate-stimulation
#1
Mohanad H Nada, Hong Wang, Grefachew Workalemahu, Yoshimasa Tanaka, Craig T Morita
BACKGROUND: Human γδ T cells expressing Vγ2Vδ2 T cell receptors monitor foreign- and self-prenyl pyrophosphate metabolites in isoprenoid biosynthesis to mediate immunity to microbes and tumors. Adoptive immunotherapy with Vγ2Vδ2 T cells has been used to treat cancer patients with partial and complete remissions. Most clinical trials and preclinical studies have used continuous zoledronate exposure to expand Vγ2Vδ2 cells where zoledronate is slowly diluted over the course of the culture...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28228283/adipose-type-one-innate-lymphoid-cells-regulate-macrophage-homeostasis-through-targeted-cytotoxicity
#2
Selma Boulenouar, Xavier Michelet, Danielle Duquette, David Alvarez, Andrew E Hogan, Christina Dold, Donal O'Connor, Suzanne Stutte, Ali Tavakkoli, Desmond Winters, Mark A Exley, Donal O'Shea, Michael B Brenner, Ulrich von Andrian, Lydia Lynch
Adipose tissue has a dynamic immune system that adapts to changes in diet and maintains homeostatic tissue remodeling. Adipose type 1 innate lymphoid cells (AT1-ILCs) promote pro-inflammatory macrophages in obesity, but little is known about their functions at steady state. Here we found that human and murine adipose tissue harbor heterogeneous populations of AT1-ILCs. Experiments using parabiotic mice fed a high-fat diet (HFD) showed differential trafficking of AT1-ILCs, particularly in response to short- and long-term HFD and diet restriction...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28222841/phenotypic-and-functional-characterization-of-peripheral-blood-lymphocytes-from-various-age-and-sex-specific-groups-of-owl-monkeys-aotus-nancymaae
#3
Pramod N Nehete, Bharti P Nehete, Sriram Chitta, Lawrence E Williams, Christian R Abee
Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model for human disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys...
February 1, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28222752/dendritic-cells-macrophages-nk-and-cd8-t-lymphocytes-play-pivotal-roles-in-controlling-hsv-1-in-the-trigeminal-ganglia-by-producing-il1-beta-inos-and-granzyme-b
#4
Natália Lucinda, Maria Marta Figueiredo, Natália Lima Pessoa, Beatriz Senra Álvares da Silva Santos, Graciela Kunrath Lima, Arthur Molinari Freitas, Alexandre Magalhães Vieira Machado, Erna Geessien Kroon, Lis Ribeiro do Valle Antonelli, Marco Antônio Campos
BACKGROUND: Herpes simplex virus type 1 (HSV-1) cause not only mild symptoms but also blindness and encephalitis. It was previously shown that the immune response against HSV-1 occurs mainly in the trigeminal ganglia (TG) and that Toll-like receptors 2 and 9 (TLR2/9) are important in mediating this response. It was also demonstrated that iNOS (nitric oxide synthase) and interleukin 1 beta (IL-1β) play an essential role in the defense against HSV-1 infection. Importantly, the present work aimed to identify the primary cells responsible for iNOS and IL-1β production and search for other important molecules and cells that might or might not depend on TLR2/9 receptors to mediate the immune response against HSV-1...
February 21, 2017: Virology Journal
https://www.readbyqxmd.com/read/28222146/cytotoxic-effector-functions-of-t-cells-are-not-required-for-protective-immunity-against-fatal-rickettsia-typhi-infection-in-a-murine-model-of-infection-role-of-th1-and-th17-cytokines-in-protection-and-pathology
#5
Kristin Moderzynski, Liza Heine, Jessica Rauch, Stefanie Papp, Svenja Kuehl, Ulricke Richardt, Bernhard Fleischer, Anke Osterloh
Endemic typhus caused by Rickettsia (R.) typhi is an emerging febrile disease that can be fatal due to multiple organ pathology. Here we analyzed the requirements for protection against R. typhi by T cells in the CB17 SCID model of infection. BALB/c wild-type mice generate CD4+ TH1 and cytotoxic CD8+ T cells both of which are sporadically reactivated in persistent infection. Either adoptively transferred CD8+ or CD4+ T cells protected R. typhi-infected CB17 SCID mice from death and provided long-term control...
February 21, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28219704/%C3%AE-lactam-hypersensitivity-involves-expansion-of-circulating-and-skin-resident-th22-cells
#6
Andrew Sullivan, Eryi Wang, John Farrell, Paul Whitaker, Lee Faulkner, Daniel Peckham, B Kevin Park, Dean J Naisbitt
BACKGROUND: β-lactam hypersensitivity has been classified according to the phenotype and function of drug-specific T-cells; however, new T-cell subsets have not been considered. OBJECTIVE: The objective of this study was use piperacillin as a model of β-lactam hypersensitivity to study the nature of the drug-specific T-cell response induced in the blood and skin of hypersensitive patients and healthy volunteers. METHODS: Drug-specific T-cells were cloned from blood and inflamed skin and cellular phenotype and function was explored...
February 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28216374/yin-yang-effect-of-tumor-infiltrating-b-cells-in-breast-cancer-from-mechanism-to-immunotherapy
#7
Zhigang Zhang, Ying Zhu, Zhen Wang, Ting Zhang, Pin Wu, Jian Huang
Breast cancer cells secrete chemokines, such as CXCL13, and antigens or express high endothelial venules, attracting B cells to infiltrate into the tumor microenvironment and play a "yin-yang" effect. They not only enhance the anti-tumor immune effect via secreting antibodies and influencing the Fas/FasL, CXCR4/CXCL12 and perforin pathways but they also promote the tumor to form a suppressive milieu by producing immunomodulatory factors and cytokines or using cell-to-cell education to induce the generation of Tregs or myeloid-derived suppressor cells (MDSCs)...
February 16, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#8
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28213049/impaired-nk-cell-functionality-and-increased-tnf-%C3%AE-production-as-biomarkers-of-chronic-chikungunya-arthritis-and-rheumatoid-arthritis
#9
Subrat Thanapati, Mohini Ganu, Prashant Giri, Shruti Kulkarni, Meenal Sharma, Prasad Babar, Ashok Ganu, Anuradha S Tripathy
The chronic chikungunya arthritis symptoms closely mimic the rheumatoid arthritis (RA) symptoms, thus making it difficult to distinguish between these two clinical entities. The current comparative study characterizes NK (CD3(-)CD56(+)) and NK-like T (CD3(+)CD56(+)) cell responses in patients with chronic chikungunya arthritis and RA. Phenotype and functions of NK and NK-like T cells repertoire were assessed in 56 chronic chikungunya arthritis, 26 RA patients and 82 controls using flow cytometry. TNF-α and IFN-γ-secreting NK-like T cells were high in both chronic arthritis patients than in controls...
February 14, 2017: Human Immunology
https://www.readbyqxmd.com/read/28197386/deficiency-of-the-immunostimulatory-cytokine-il-21-promotes-intestinal-neoplasia-via-dysregulation-of-the-th1-th17-axis
#10
Mia Shapiro, Bisweswar Nandi, Gabriel Gonzalez, Rao H Prabhala, Hiroshi Mashimo, Qin Huang, Natasha Y Frank, Nikhil C Munshi, Jason S Gold
IL-21 has reported activity in promoting both Th1 and Th17 immune responses. Its role in sporadic human colorectal cancer is unknown. We aimed to delineate the role of IL-21 in a model of sporadic intestinal carcinogenesis. We found that in APC(MIN/+) mice, ablation of IL-21 increased intestinal tumorigenesis. Expression of pro-inflammatory Th17-associated genes, including RORγt and IL-17A, was increased in the intestine in the absence of IL-21, while expression of antitumor Th1-associated genes Tbet, IFNγ, granzyme B, and perforin was decreased...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196960/repair-of-a-bacterial-small-%C3%AE-barrel-toxin-pore-depends-on-channel-width
#11
Gisela von Hoven, Amable J Rivas, Claudia Neukirch, Martina Meyenburg, Qianqian Qin, Sapun Parekh, Nadja Hellmann, Matthias Husmann
Membrane repair emerges as an innate defense protecting target cells against bacterial pore-forming toxins. Here, we report the first paradigm of Ca(2+)-dependent repair following attack by a small β-pore-forming toxin, namely, plasmid-encoded phobalysin of Photobacterium damselae subsp. damselae In striking contrast, Vibrio cholerae cytolysin, the closest ortholog of phobalysin, subverted repair. Mutational analysis uncovered a role of channel width in toxicity and repair. Thus, the replacement of serine at phobalysin´s presumed channel narrow point with the bulkier tryptophan, the corresponding residue in Vibrio cholerae cytolysin (W318), modulated Ca(2+) influx, lysosomal exocytosis, and membrane repair...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28193831/%C3%AE-2-glycoprotein-i-recognition-drives-th1-inflammation-in-atherosclerotic-plaques-of-patients-with-primary-antiphospholipid-syndrome
#12
Marisa Benagiano, Maria Gerosa, Jacopo Romagnoli, Michael Mahler, Maria O Borghi, Alessia Grassi, Chiara Della Bella, Giacomo Emmi, Amedeo Amedei, Elena Silvestri, Lorenzo Emmi, Domenico Prisco, Pier Luigi Meroni, Mario M D'Elios
Antiphospholipid syndrome (APS) is characterized by recurrent arterial/venous thrombosis and miscarriages in the persistent presence of autoantibodies against phospholipid-binding proteins (aPLs), such as β2 glycoprotein I (β2GPI). In addition to the aPL thrombophilic effect, arterial thrombosis was related to accelerated atherosclerosis in animal models; however, contrasting findings were reported in primary APS patients with regard to the increased number of plaques or abnormal arterial wall thickness. We investigated the cytokine production induced by β2GPI in activated T cells that infiltrate in vivo atherosclerotic lesions of primary APS patients with atherothrombosis...
February 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28170096/circulating-nk-cells-and-their-subsets-in-beh%C3%A3-et-s-disease
#13
Md Samiul Hasan, Paul L Ryan, Lesley A Bergmeier, Farida Fortune
Behçet's Disease (BD) is an auto-inflammatory, chronic relapsing/remitting disease of unknown aetiology with both innate and acquired immune cells implicated in disease pathogenesis. Peripheral blood Natural Killer (NK) cells and their CD56(Dim) /CD56(Bright) subsets were surface phenotyped using CD27 and CD16 surface markers in 60 BD patients compared to 60 healthy controls (HCs). Functional potential was assessed by production of interferon (IFN)-γ, Granzyme B, Perforin and the expression of degranulation marker CD107a...
February 7, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28166682/clonally-expanded-cytotoxic-cd4-t-cells-and-the-pathogenesis-of-igg4-related-disease
#14
Hamid Mattoo, John H Stone, Shiv Pillai
IgG4-related disease (IgG4-RD) is a systemic condition of unknown cause characterized by highly fibrotic lesions, with dense lymphoplasmacytic infiltrates containing a preponderance of IgG4-expressing plasma cells. CD4(+) T cells and B cells constitute the major inflammatory cell populations in IgG4-RD lesions. IgG4-RD patients with active, untreated disease show a marked expansion of plasmablasts in the circulation. Although the therapeutic depletion of B cells suggests a role for these cells in the disease, a direct role for B cells or IgG4 in the pathogenesis of IgG4-RD is yet to be demonstrated...
February 2017: Autoimmunity
https://www.readbyqxmd.com/read/28166206/real-time-visualization-of-perforin-nanopore-assembly
#15
Carl Leung, Adrian W Hodel, Amelia J Brennan, Natalya Lukoyanova, Sharon Tran, Colin M House, Stephanie C Kondos, James C Whisstock, Michelle A Dunstone, Joseph A Trapani, Ilia Voskoboinik, Helen R Saibil, Bart W Hoogenboom
Perforin is a key protein of the vertebrate immune system. Secreted by cytotoxic lymphocytes as soluble monomers, perforin can self-assemble into oligomeric pores of 10-20 nm inner diameter in the membranes of virus-infected and cancerous cells. These large pores facilitate the entry of pro-apoptotic granzymes, thereby rapidly killing the target cell. To elucidate the pathways of perforin pore assembly, we carried out real-time atomic force microscopy and electron microscopy studies. Our experiments reveal that the pore assembly proceeds via a membrane-bound prepore intermediate state, typically consisting of up to approximately eight loosely but irreversibly assembled monomeric subunits...
February 6, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28153802/impairment-of-peripheral-vdelta2-t-cells-in-human-cystic-echinococcosis
#16
Hao Wang, Ming Li, Xiaoxia Zhang, Fang He, Shengbin Zhang, Jiaqing Zhao
Cystic echinococcosis (CE) induced by metacestodes (larval stages) of Echinococcus granulosus (E.granulosus) represents a severe endemic disease worldwide. Gamma delta (γδ) T cells, one of innate immune cells, play pivotal role in pathogenic infections. However, whether γδ T cells are involved in CE remains unclear. This study firstly investigated the role of peripheral γδ T cells in CE. The results showed that the percentage of peripheral γδ T cells from CE patients was decreased, compared with healthy controls (HC) (p < 0...
January 31, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28137589/participation-of-perforin-in-mediating-dopaminergic-neuron-loss-in-mptp-induced-parkinson-s-disease-in-mice
#17
Su-Ping Peng, Ye Zhang, Sjef Copray, Melitta Schachner, Yan-Qin Shen
Both resident innate and peripheral immune aberrations have been demonstrated to influence Parkinson's disease (PD) progression. However, it is still enigmatic how and which immune components are lethal to the dopaminergic neuron in PD. We now show that levels of perforin, a pore-forming protein expressed in cytotoxic immune cells, was significantly increased in the serum of wild-type mice 4 weeks after injection of MPTP, a toxin used to induce PD-like symptoms. We demonstrate that perforin-deficiency attenuated the acute striatal dopamine reduction by 33%, ablated microglia activation 3 days post MPTP-injection; and retarded dopaminergic neuron death 4 weeks post MPTP-injection...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28130139/structural-effects-of-sulfated-polysaccharides-from-codium-fragile-on-nk-cell-activation-and-cytotoxicity
#18
Utoomporn Surayot, SangGuan You
The effects of sulfates and proteins of the sulfated polysaccharide-F2 (SP-F2) from Codium fragile on the NK cell activation and cytotoxicity were systematically investigated. The SP-F2 treatment significantly increased both NK cell proliferation (129%/100μg/mL) and their potent cytotoxic effects against HeLa cells (46%). The SP-F2 treatment appeared to enhance NK cell activation through the expression of the activating receptor, NKp30; the secretion of the cytokine, IFN-γ and the release of the lysing proteins, perforin and granzyme-B...
January 24, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28122453/improving-t-cell-expansion-with-a-soft-touch
#19
Lester H Lambert, Geraldine K E Goebrecht, Sarah E De Leo, Roddy S O'Connor, Selene Nunez-Cruz, Tai-De Li, Jinglun Yuan, Michael C Milone, Lance C Kam
Protein-coated microbeads provide a consistent approach for activating and expanding populations of T cells for immunotherapy but do not fully capture the properties of antigen presenting cells. In this report, we enhance T cell expansion by replacing the conventional, rigid bead with a mechanically soft elastomer. Polydimethylsiloxane (PDMS) was prepared in a microbead format and modified with activating antibodies to CD3 and CD28. A total of three different formulations of PDMS provided an extended proliferative phase in both CD4(+)-only and mixed CD4(+)-CD8(+) T cell preparations...
January 30, 2017: Nano Letters
https://www.readbyqxmd.com/read/28120745/phenotypic-and-functional-characterization-of-peripheral-blood-lymphocytes-from-various-age-and-sex-specific-groups-of-owl-monkeys-aotus-nancymaae
#20
Pramod N Nehete Bharti P Nehete Sriram Chitta Lawrence E Williams And Christian R Abee
Owl monkeys (Aotus nancymaae) are New World NHP that serve an important role in vaccine development and as a model forhuman disease conditions such as malaria. Despite the past contributions of this animal model, limited information is available about the phenotype and functional properties of peripheral blood lymphocytes in reference to sex and age. Using a panel of human antibodies and a set of standardized human immune assays, we identified and characterized various peripheral blood lymphocyte subsets, evaluated the immune functions of T cells, and analyzed cytokines relative to sex and age in healthy owl monkeys...
January 24, 2017: Comparative Medicine
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