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Journal of Immunology: Official Journal of the American Association of Immunologists

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https://www.readbyqxmd.com/read/30012850/influenza-a-virus-negative-strand-rna-is-translated-for-cd8-t-cell-immunosurveillance
#1
Heather D Hickman, Jacqueline W Mays, James Gibbs, Ivan Kosik, Javier G Magádan, Kazuyo Takeda, Suman Das, Glennys V Reynoso, Barbara F Ngudiankama, JiaJie Wei, John P Shannon, Daniel McManus, Jonathan W Yewdell
Probing the limits of CD8+ T cell immunosurveillance, we inserted the SIINFEKL peptide into influenza A virus (IAV)-negative strand gene segments. Although IAV genomic RNA is considered noncoding, there is a conserved, relatively long open reading frame present in segment 8, encoding a potential protein termed NEG8. The biosynthesis of NEG8 from IAV has yet to be demonstrated. Although we failed to detect NEG8 protein expression in IAV-infected mouse cells, cell surface Kb -SIINFEKL complexes are generated when SIINFEKL is genetically appended to the predicted C terminus of NEG8, as shown by activation of OT-I T cells in vitro and in vivo...
July 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30012849/2b4-mediates-inhibition-of-cd8-t-cell-responses-via-attenuation-of-glycolysis-and-cell-division
#2
Sonia J Laurie, Danya Liu, Maylene E Wagener, Phoebe C Stark, Cox Terhorst, Mandy L Ford
We recently showed that 2B4 expression on memory T cells in human renal transplant recipients was associated with reduced rates of rejection. To investigate whether 2B4 functionally underlies graft acceptance during transplantation, we established an experimental model in which 2B4 was retrogenically expressed on donor-reactive murine CD8+ T cells (2B4rg), which were then transferred into naive recipients prior to skin transplantation. We found that constitutive 2B4 expression resulted in significantly reduced accumulation of donor-reactive CD8+ T cells following transplantation and significantly prolonged graft survival following transplantation...
July 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30012848/b-cell-defects-observed-in-nod2-knockout-mice-are-a-consequence-of-a-dock2-mutation-frequently-found-in-inbred-strains
#3
Serre-Yu Wong, Maryaline Coffre, Deepshika Ramanan, Marcus J Hines, Luis E Gomez, Lauren A Peters, Eric E Schadt, Sergei B Koralov, Ken Cadwell
Phenotypic differences among substrains of laboratory mice due to spontaneous mutations or pre-existing genetic variation confound the interpretation of targeted mutagenesis experiments and contribute to challenges with reproducibility across institutions. Notably, C57BL/6 Hsd mice and gene-targeted mice that have been backcrossed to this substrain have been reported to harbor a duplication in exons 28 and 29 of Dock2 In this study, we demonstrate the presence of this Dock2 variant in the widely used Nod2 -/- mice...
July 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30012847/mir-340-alleviates-psoriasis-in-mice-through-direct-targeting-of-il-17a
#4
Jiang Bian, Ruiling Liu, Tingting Fan, Lijuan Liao, Shaowen Wang, Wenwen Geng, Ting Wang, Weiyun Shi, Qingguo Ruan
Th17 cell is a well-known lineage of CD4+ effector Th cells that selectively produce IL-17A and play critical roles during the pathogenesis of autoimmune disease. A microRNA (miRNA) is a small noncoding RNA molecule that functions in posttranscriptional regulation of gene expression. Recently, an increasing number of studies have demonstrated that multiple miRNAs are dysregulated in patients with various autoimmune diseases and mediate autoimmune disease pathologic condition at least in part through the regulation of Th17 response...
July 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30012846/id3-restricts-%C3%AE-%C3%AE-nkt-cell-expansion-by-controlling-egr2-and-c-myc-activity
#5
Baojun Zhang, Anjun Jiao, Meifang Dai, David L Wiest, Yuan Zhuang
γδ NKT cells are neonatal-derived γδ T lymphocytes that are grouped together with invariant NKT cells based on their shared innate-like developmental program characterized by the transcription factor PLZF (promyelocytic leukemia zinc finger). Previous studies have demonstrated that the population size of γδ NKT cells is tightly controlled by Id3-mediated inhibition of E-protein activity in mice. However, how E proteins promote γδ NKT cell development and expansion remains to be determined. In this study, we report that the transcription factor Egr2, which also activates PLZF expression in invariant NKT cells, is essential for regulating γδ NKT cell expansion...
July 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30006377/effector-t-cell-resistance-to-suppression-and-stat3-signaling-during-the-development-of-human-type-1-diabetes
#6
Emmi-Leena Ihantola, Tyyne Viisanen, Ahmad M Gazali, Kirsti Näntö-Salonen, Auni Juutilainen, Leena Moilanen, Reeta Rintamäki, Jussi Pihlajamäki, Riitta Veijola, Jorma Toppari, Mikael Knip, Jorma Ilonen, Tuure Kinnunen
Dysregulation of regulatory T cell (Treg)-mediated suppression and, in particular, resistance of CD4+ effector T cells (Teffs) to suppression have been implicated in the pathogenesis of human type 1 diabetes (T1D). However, the mechanistic basis behind this resistance and the time frame during which it develops in relation to the onset of clinical T1D remain unclear. In this study, we analyzed the capacity of peripheral blood Teffs isolated both from patients with T1D and from prediabetic at-risk subjects positive for multiple diabetes-associated autoantibodies (AAb+ ) to be suppressed by Tregs...
July 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30006376/correction-both-hiv-infected-and-uninfected-cells-express-trailshort-which-confers-trail-resistance-upon-bystander-cells-within-the-microenvironment
#7
Zilin Nie, Fatma Aboulnasr, Sekar Natesampillai, Stephen P Burke, Ashton Krogman, Gary D Bren, Thomas D Y Chung, Jeff R Anderson, Michele K Smart, David J Katzmann, Govindarajan Rajagopalan, Nathan W Cummins, Andrew D Badley
No abstract text is available yet for this article.
July 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30006375/il-7-enables-antibody-responses-to-bacterial-polysaccharides-by-promoting-b-cell-receptor-diversity
#8
Gregory S Dickinson, Eric A Levenson, Justin A Walker, John F Kearney, Kishore R Alugupalli
Polysaccharide vaccines such as the Vi polysaccharide (ViPS) of Salmonella enterica serovar Typhi induce efficient Ab responses in adults but not in young children. The reasons for this difference are not understood. IL-7 dependency in B cell development increases progressively with age. IL-7Rα-mediated signals are required for the expression of many VH gene segments that are distal to DH -JH in the IgH locus and for the complete diversification of the BCR repertoire. Therefore, we hypothesized that B cells generated in the absence of IL-7 do not recognize a wide range of Ags because of a restricted BCR repertoire...
July 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30006374/qualified-biolayer-interferometry-avidity-measurements-distinguish-the-heterogeneity-of-antibody-interactions-with-plasmodium-falciparum-circumsporozoite-protein-antigens
#9
S Moses Dennison, Matthew Reichartz, Kelly E Seaton, Sheetij Dutta, Ulrike Wille-Reece, Adrian V S Hill, Katie J Ewer, Wes Rountree, Marcella Sarzotti-Kelsoe, Daniel A Ozaki, S Munir Alam, Georgia D Tomaras
Ab avidity is a measure of the overall strength of Ab-Ag interactions and hence is important for understanding the functional efficiency of Abs. In vaccine evaluations, Ab avidity measurements can provide insights into immune correlates of protection and generate hypotheses regarding mechanisms of protection to improve vaccine design to achieve higher levels of efficacy. The commonly used Ab avidity assays require the use of chaotropic reagents to measure avidity index. In this study, using real-time detection of Ab-Ag binding by biolayer interferometry (BLI) technique, we have developed a qualified assay for measuring avidity of vaccine-induced Abs specific for Plasmodium falciparum circumsporozoite protein (CSP) Ags...
July 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29997126/the-splicing-factor-rna-binding-fox-protein-1-mediates-the-cellular-immune-response-in-drosophila-melanogaster
#10
Ashley E Nazario-Toole, Javier Robalino, Kwame Okrah, Hector Corrada-Bravo, Stephen M Mount, Louisa P Wu
The uptake and destruction of bacteria by phagocytic cells is an essential defense mechanism in metazoans. To identify novel genes involved in the phagocytosis of Staphylococcus aureus , a major human pathogen, we assessed the phagocytic capacity of adult blood cells (hemocytes) of the fruit fly, Drosophila melanogaster, by testing several lines of the Drosophila Genetic Reference Panel. Natural genetic variation in the gene RNA-binding Fox protein 1 ( Rbfox1 ) correlated with low phagocytic capacity in hemocytes, pointing to Rbfox1 as a candidate regulator of phagocytosis...
July 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29997125/shaving-is-an-epiphenomenon-of-type-i-and-ii-anti-cd20-mediated-phagocytosis-whereas-antigenic-modulation-limits-type-i-monoclonal-antibody-efficacy
#11
Lekh N Dahal, Chie-Yin Huang, Richard J Stopforth, Abbie Mead, Keith Chan, Juliet X Bowater, Martin C Taylor, Priyanka Narang, H T Claude Chan, Jinny H Kim, Andrew T Vaughan, Francesco Forconi, Stephen A Beers
Rituximab is an anti-CD20 mAb used in the treatment of B cell malignancies. Loss of surface CD20 Ag from the surface of target cells is thought to be one mechanism governing resistance to rituximab, but how this occurs is not completely understood. Two explanations for this have been proposed: antigenic modulation whereby mAb:CD20 complexes are internalized in a B cell intrinsic process and shaving, in which mAb:CD20 complexes undergo trogocytic removal by effector cells, such as macrophages. However, there is conflicting evidence as to which predominates in clinical scenarios and hence the best strategies to overcome resistance...
July 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29997124/tumor-dendritic-cells-dcs-derived-from-precursors-of-conventional-dcs-are-dispensable-for-intratumor-ctl-responses
#12
Jun Diao, Hongtao Gu, Michael Tang, Jun Zhao, Mark S Cattral
The success of adoptive CTL therapy for cancer depends on interactions between tumor-infiltrating CTLs and cancer cells as well as other cells and molecules in the tumor microenvironment. Tumor dendritic cells (DCs) comprise several subsets: CD103+ CD11b- DC1 and CD11b+ CD64- DC2, which originate from circulating precursors of conventional DCs, and CD11b+ CD64+ DC3, which arise from monocytes. It remains controversial which of these subset(s) promotes intratumor CTL proliferation, expansion, and function. To address this issue, we used the Zbtb46-DTR-transgenic mouse model to selectively deplete DC1 and DC2 from tumors and lymphoid tissues...
July 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29997123/cd4-regulatory-t-cells-exert-differential-functions-during-early-and-late-stages-of-the-immune-response-to-respiratory-viruses
#13
Meredith C Rogers, Kristina D Lamens, Nazly Shafagati, Monika Johnson, Tim D Oury, Sebastian Joyce, John V Williams
Acute respiratory virus infection (ARI) induces CD8+ T cells with diminished cytokine production and functional impairment. The role of cellular mediators of immune impairment, specifically CD4+ regulatory T cells (Tregs), is incompletely understood in ARI. Tregs are known suppressors of effector T cell function, but whether they are detrimental or beneficial in ARI remains controversial. We show in this paper that Treg depletion leads to increased CD8+ T cell function and lower virus titer in mice infected with human metapneumovirus...
July 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29997122/functional-evidence-of-pulmonary-extracellular-vesicles-in-infectious-and-noninfectious-lung-inflammation
#14
Heedoo Lee, Duo Zhang, Debra L Laskin, Yang Jin
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a highly complex process that can be triggered by both noninfectious (sterile) and infectious stimuli. Inflammatory lung responses are one of the key features in the pathogenesis of this devastating syndrome. How ALI/ARDS-associated inflammation develops remains incompletely understood, particularly after exposure to sterile stimuli. Emerging evidence suggests that extracellular vesicles (EVs) regulate intercellular communication and inflammatory responses in various diseases...
July 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29987163/a-tolerogenic-artificial-apc-durably-ameliorates-experimental-autoimmune-encephalomyelitis-by-directly-and-selectively-modulating-myelin-peptide-autoreactive-cd4-and-cd8-t-cells
#15
Xin Wan, Weiya Pei, Khawar Ali Shahzad, Lei Zhang, Shilong Song, Xiaoxiao Jin, Limin Wang, Chen Zhao, Chuanlai Shen
In this study, a tolerogenic artificial APC (TaAPC) was developed to directly and selectively modulate myelin-autoreactive CD4+ and CD8+ T cells in the myelin oligodendrocyte glycoprotein (MOG)35-55 peptide-induced experimental autoimmune encephalomyelitis in C57BL/6J mice. Cell-sized polylactic-coglycolic acid microparticles were generated to cocouple target Ags (MOG40-54 /H-2Db -Ig dimer, MOG35-55 /I-Ab multimer), regulatory molecules (anti-Fas and PD-L1-Fc), and "self-marker" CD47-Fc and encapsulate inhibitory cytokine (TGF-β1)...
July 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29987162/cx-3-cr1-macrophages-and-cd8-t-cells-control-intestinal-iga-production
#16
Young-In Kim, Joo-Hye Song, Hyun-Jeong Ko, Mi-Na Kweon, Chang-Yuil Kang, Hans-Christian Reinecker, Sun-Young Chang
Secretory IgA is a key host defense mechanism that controls the intestinal microbiota. We investigated the role of CD11c+ CX3 CR1+ CD64+ macrophages in IgA production in the intestine. Intestinal CX3 CR1+ macrophages directly induced IgA secretion by B cells. Ag delivery to lamina propria (LP) CX3 CR1+ macrophages specifically induced intestinal IgA production. The induction of IgA by CX3 CR1+ macrophages required BAFF, a proliferation-inducing ligand, and TNF-α, but was surprisingly independent of TLR-mediated microbial recognition and retinoic acid signaling...
July 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29987161/role-of-peptidylarginine-deiminase-4-in-neutrophil-extracellular-trap-formation-and-host-defense-during-klebsiella-pneumoniae-induced-pneumonia-derived-sepsis
#17
Theodora A M Claushuis, Lieve E H van der Donk, Anna L Luitse, Henk A van Veen, Nicole N van der Wel, Lonneke A van Vught, Joris J T H Roelofs, Onno J de Boer, Jacqueline M Lankelma, Louis Boon, Alex F de Vos, Cornelis van 't Veer, Tom van der Poll
Peptidylarginine deiminase 4 (PAD4) catalyzes citrullination of histones, an important step for neutrophil extracellular trap (NET) formation. We aimed to determine the role of PAD4 during pneumonia. Markers of NET formation were measured in lavage fluid from airways of critically ill patients. NET formation and host defense were studied during pneumonia-derived sepsis caused by Klebsiella pneumoniae in PAD4+/+ and PAD4-/- mice. Patients with pneumosepsis, compared with those with nonpulmonary disease, showed increased citrullinated histone 3 (CitH3) levels in their airways and a trend toward elevated levels of NET markers cell-free DNA and nucleosomes...
July 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29987160/cracr2a-mediated-tcr-signaling-promotes-local-effector-th1-and-th17-responses
#18
Jin Seok Woo, Sonal Srikanth, Kyun-Do Kim, Heidi Elsaesser, Jing Lu, Matteo Pellegrini, David G Brooks, Zuoming Sun, Yousang Gwack
Ca2+ release-activated Ca2+ channel regulator 2A (CRACR2A) is expressed abundantly in T cells and acts as a signal transmitter between TCR stimulation and activation of the Ca2+ /NFAT and JNK/AP1 pathways. CRACR2A has been linked to human diseases in numerous genome-wide association studies and was shown to be one of the most sensitive targets of the widely used statin drugs. However, the physiological role of CRACR2A in T cell functions remains unknown. In this study, using transgenic mice for tissue-specific deletion, we show that CRACR2A promotes Th1 responses and effector function of Th17 cells...
July 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29980613/type-1-ifn-induction-by-cytosolic-nucleic-acid-is-intact-in-neonatal-mononuclear-cells-contrasting-starkly-with-neonatal-hyporesponsiveness-to-tlr-ligation-due-to-independence-from-endosome-mediated-irf3-activation
#19
Kiva Brennan, Bobby D O'Leary, Danielle Mc Laughlin, Eamon P Breen, Emma Connolly, Nusrat Ali, David N O'Driscoll, Ema Ozaki, Rebecca Mahony, Kelly Mulfaul, Aoife M Ryan, Aine Ni Chianain, Alison McHugh, Eleanor J Molloy, Andrew E Hogan, Sri Paran, Fionnuala M McAuliffe, Sarah L Doyle
Two million infants die each year from infectious diseases before they reach 12 mo; many of these diseases are vaccine preventable in older populations. Pattern recognition receptors represent the critical front-line defense against pathogens. Evidence suggests that the innate immune system does not fully develop until puberty, contributing to impaired response to infection and impaired vaccine responses in neonates, infants, and children. The activity of the pattern recognition receptor family of cytosolic nucleic acid (CNA) sensors in this pediatric population has not been reported...
July 6, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29980612/isotype-switched-autoantibodies-are-necessary-to-facilitate-central-nervous-system-autoimmune-disease-in-aicda-and-ung-mice
#20
Georgina Galicia, Dennis S W Lee, Valeria Ramaglia, Lesley A Ward, Jennifer Y Yam, Leslie Y T Leung, Rui Li, Marcus Handy, Junxian Zhang, Paulina C Drohomyrecky, Eric Lancaster, Amit Bar-Or, Alberto Martin, Jennifer L Gommerman
B cell-depleting therapies have been shown to ameliorate symptoms in multiple sclerosis (MS) patients; however, the mechanism of action remains unclear. Following priming with Ag, B cells undergo secondary diversification of their BCR, including BCR class-switch recombination (CSR) and somatic hypermutation (SHM), with both processes requiring the enzyme activation-induced (cytidine) deaminase. We previously reported that activation-induced (cytidine) deaminase is required for full clinical manifestation of disease in an animal model of MS (experimental autoimmune encephalomyelitis; EAE) provoked by immunization with the extracellular domain of recombinant human myelin oligodendrocyte glycoprotein (hMOG)...
July 6, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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