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Immunology

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https://www.readbyqxmd.com/read/28211040/anti-cd3-treatment-upregulates-pd-1-expression-on-activated-effector-t-cells-and-severely-impairs-their-inflammatory-capacity
#1
Maja Wallberg, Asha Recino, Jenny Phillips, Duncan Howie, Margaux Vienne, Christopher Paluch, Miyuki Azuma, F Susan Wong, Herman Waldmann, Anne Cooke
T cells play a key role in the pathogenesis of type 1 diabetes, and targeting the CD3 component of the TCR complex provides one therapeutic approach. Anti-CD3 treatment can reverse overt disease in spontaneously diabetic non-obese diabetic mice, an effect proposed to, at least in part, be caused by a selective depletion of pathogenic cells. We have used a transfer model to further investigate the effects of anti-CD3 treatment on green fluorescent protein (GFP)(+) islet-specific effector T cells in vivo. The GFP expression allowed us to isolate the known effectors at different time points during treatment to assess cell presence in various organs as well as gene expression and cytokine production...
February 17, 2017: Immunology
https://www.readbyqxmd.com/read/28207945/cd4-cd25-garp-tregs-display-a-compromised-suppressive-function-in-patients-with-dilated-cardiomyopathy
#2
Yuzhen Wei, Kunwu Yu, Hui Wei, Xin Su, Ruirui Zhu, Huairui Shi, Haitao Sun, Quan Luo, Wenbin Xu, Junhui Xiao, Yucheng Zhong, Qiutang Zeng
Dilated cardiomyopathy (DCM) is a lethal inflammatory heart disease and closely connected with dysfunction of the immune system. Glycoprotein -A repetitions predominant (GARP) expressed on activated CD4(+) T cells with suppressive activity has been established. This study aimed to investigate the frequency and function of circulating CD4(+) CD25(+) GARP(+) regulatory T cells (Tregs) in DCM. 45 DCM patients and 46 controls were enrolled in this study. There was a significant increase in peripheral Th1 and Th17 number and their related cytokines (IFN-γ, IL-17), and an obvious decrease in Treg number, TGF-β1 levels and the expression of FOXP3 and GARP in patients with DCM as compared with controls...
February 16, 2017: Immunology
https://www.readbyqxmd.com/read/28207940/structural-and-functional-changes-to-lymph-nodes-in-ageing-mice
#3
Vivian M Turner, Neil A Mabbott
Lymph nodes (LN) are secondary lymphoid organs spread throughout the lymphatic system. They function to filter pathogenic material from the lymphatic fluid to maintain the health of the organism. Subcapsular sinus macrophages (SCSM) are amongst the first-responders within the LN due to their strategic location within the subcapsular sinus region. These macrophages aid the delivery of immune complexes to B cells and follicular dendritic cells (FDC) within the LN. Here we show an increase in SCSM and other macrophage populations within aged LN...
February 16, 2017: Immunology
https://www.readbyqxmd.com/read/28201853/antigenic-cross-reactivity-between-schistosoma-mansoni-and-peanut-a-role-for-cross-reactive-carbohydrate-determinants-ccds-and-implications-for-the-hygiene-hypothesis
#4
Joseph E Igetei, Marwa El-Faham, Susan Liddell, Michael J Doenhoff
The antigenic reactivity of constituents of Schistosoma mansoni and peanut (Arachis hypogaea) was investigated to determine whether identical antigenic epitopes possessed by both organisms provided a possible explanation for the negative correlation between chronic schistosome infection and atopy to allergens. Aqueous extracts of peanuts were probed in Western immunoblots with rabbit IgG antibodies raised against the egg, cercarial and adult worm stages of S. mansoni. Several molecules in the peanut extract were antigenically reactive with antibodies from the various rabbit anti-schistosome sera...
February 15, 2017: Immunology
https://www.readbyqxmd.com/read/28190273/priming-with-high-and-low-respiratory-allergen-dose-induces-differential-cd4-th2-cells-and-ige-igg1-antibody-responses-in-mice
#5
Kazuki Furuhashi, Yen L Chua, Kenneth H S Wong, Qian Zhou, Debbie C P Lee, Ka H Liong, Guo H Teo, Paul E Hutchinson, David M Kemeny
Sensitization of allergic patients normally takes place over several years and is the result of repeated exposure to low levels of allergen. Most mouse asthma models use a high dose of allergen administered over a short period. We have investigated the role of dose in the immune response to an inhaled respiratory allergen (Blomia tropicalis). We observed the effect of priming dose on the allergic response in mice intranasally immunized with low (0.5μg) and high dose (50μg) of B. tropicalis extract and sacrificed one day after the last challenge...
February 11, 2017: Immunology
https://www.readbyqxmd.com/read/28190271/increased-ctla-4-t-cells-may-contribute-to-impaired-th1-immune-responses-in-patients-with-chronic-obstructive-pulmonary-disease-copd
#6
Dino B A Tan, Teck-Hui Teo, Abdul M Setiawan, Nathanael E Ong, Maja Zimmermann, Patricia Price, Lea-Ann S Kirkham, Yuben P Moodley
Impaired T-helper (Th)-1 function is implicated in the susceptibility of patients with chronic obstructive pulmonary disease (COPD) to respiratory infections, which are common causes of acute exacerbations of COPD (AECOPD). To understand the underlying mechanisms, we assessed regulatory T-cells (Treg) and the expression of an inhibitory T-cell receptor, cytotoxic T-lymphocyte-associated antigen (CTLA)-4. Cryopreserved peripheral blood mononuclear cells (PBMC) from patients with AECOPD (n=17), patients with stable COPD (sCOPD; n=24) and age-matched healthy non-smoking controls (n=26) were cultured for 24hr with brefeldin-A or monensin to detect intracellular or surface CTLA-4 (respectively) by flow cytometry...
February 11, 2017: Immunology
https://www.readbyqxmd.com/read/28190264/inflammatory-stress-of-pancreatic-beta-cells-drives-release-of-extracellular-heat-shock-protein-90%C3%AE
#7
Gail J Ocaña, Liliana Pérez, Lynette Guindon, Sarah N Deffit, Carmella Evans-Molina, Debbie C Thurmond, Janice S Blum
A major obstacle in predicting and preventing the development of autoimmune type 1 diabetes (T1D) in at-risk individuals is the lack of well-established early biomarkers indicative of ongoing beta cell stress during the pre-clinical phase of disease. Recently, serum levels of the alpha cytoplasmic isoform of heat shock protein (HSP) 90 were shown to be elevated in individuals with new-onset T1D. We therefore hypothesized HSP90α could be released from beta cells in response to cellular stress and inflammation associated with the earliest stages of T1D...
February 11, 2017: Immunology
https://www.readbyqxmd.com/read/28190261/cd21int-cd23-follicular-b-cells-express-antigen-specific-secretory-igm-mrna-as-primary-and-memory-responses
#8
Qing-Hai Meng, Harry N White
CD21int/CD23+ IgM+ mouse follicular B cells comprise the bulk of the mature B cell compartment, but it is not known whether these cells contribute to the humoral antibody response. We show using a direct RT-PCR method for antigen specific VH, that FACS sorted mouse CD21int/CD23+ B cells express specific secretory IgM VH transcripts in response to immunisation and also exhibit a memory response. The secretory IgM expressed is distinct from the IgG expressed by cells of this phenotype, which we also analyse here, having a distinct broader distribution of CDR-H3 sequences and zero or low levels of somatic mutation in the region analysed...
February 11, 2017: Immunology
https://www.readbyqxmd.com/read/28185259/ips-cell-derived-gamete-associated-proteins-gaps-incite-rejection-of-ipscs-in-syngeneic-mice
#9
Eun-Mi Kim, Gohar Manzar, Nicholas Zavazava
The safety of iPS cells (iPSCs) in autologous recipients has been questioned after iPSCs, but not ES cells (ESCs), were reported to be rejected in syngeneic mice. This important topic has remained controversial because there has not been a mechanistic explanation for this phenomenon. Here, we hypothesized that iPSCs, but not ESCs, readily differentiate into gamete-forming cells that express meiotic antigens normally found in immune-privileged gonads. Because peripheral blood T cells are not tolerized to these antigens in the thymus, gamete-associated-proteins (GAPs) sensitize T cells leading to rejection...
February 10, 2017: Immunology
https://www.readbyqxmd.com/read/28140447/myeloid-derived-suppressor-cells-mediate-tolerance-induction-in-autoimmune-disease
#10
Anja Wegner, Johan Verhagen, David C Wraith
In multiple sclerosis (MS) T cells aberrantly recognise self-peptides of the myelin sheath and attack the central nervous system (CNS). Antigen-specific peptide immunotherapy, which aims to restore tolerance while avoiding the use of non-specific immunosuppressive drugs, is a promising approach to combat autoimmune disease, but the cellular mechanisms behind successful therapy remain poorly understood. Myeloid-derived suppressor cells (MDSCs) have been studied intensively in the field of cancer and to a lesser extent in autoimmunity...
January 31, 2017: Immunology
https://www.readbyqxmd.com/read/28140446/the-proportion-of-different-il-17-producing-t-cell-subsets-is-associated-with-liver-fibrosis-in-chronic-hepatitis-c
#11
Fabio C O F Cachem, Aleida S O Dias, Clarice Monteiro, José Roberto Castro, Gabriel Fernandes, Letícia Delphim, Adilson J Almeida, Felipe Tavares, Alessandra M A Maciel, Marcia M Amendola-Pires, Carlos E Brandão-Mello, Cleonice A M Bento
Studies have suggested the pivotal role of Th1-related cytokines on the outcome of HCV infection. Nevertheless, the role of different IL-17-secreting T cells on chronic hepatitis C (CHC) is less clear. Here, the in vivo IL-1β, IL-6, and IL-17 levels were positively correlated with both alanine aminotransferase (ALT) levels and hepatic lesions. When compared with the control group, CHC patients showed lower proportion of IL-17-secreting (CD4(+) and CD8(+) ) T cells capable of simultaneously producing IL-21...
January 31, 2017: Immunology
https://www.readbyqxmd.com/read/28140445/virulence-dependent-induction-of-interleukin-10-producing-tolerogenic-dendritic-cells-by-mycobacterium-tuberculosis-impedes-optimal-th1-proliferation
#12
Hongmin Kim, Kee Woong Kwon, Woo Sik Kim, Sung Jae Shin
Mycobacterium tuberculosis (Mtb) inhibits optimal Th1 responses during infection. However, the precise mechanisms by which virulent Mtb limits Th1 responses remain unclear. Here, we infected dendritic cells (DCs) with the virulent Mtb strain H37Rv or the attenuated strain H37Ra to investigate the phenotypic and functional alterations in DCs and resultant T cell responses. H37Rv-infected DCs suppressed Th1 responses more strongly than H37Ra-infected DCs. Interestingly, H37Rv, but not H37Ra, impaired DC surface molecule (CD80, CD86 and MHC class II) expression due to prominent IL-10 production while augmenting the expression of tolerogenic molecules including PD-L1, CD103, Tim-3, and indoleamine 2,3-dioxygenase (IDO) on DCs in a multiplicity-of-infection-dependent manner...
January 31, 2017: Immunology
https://www.readbyqxmd.com/read/28140444/the-nlrp3-inflammasome-contributes-to-host-protection-during-sporothrix-schenckii-infection
#13
Amanda Costa Gonçalves, Lucas Souza Ferreira, Francine Alessandra Manente, Carolina Maria Quinello Gomes de Faria, Marisa Campos Polesi, Cleverton Roberto de Andrade, Dario Simões Zamboni, Iracilda Zeppone Carlos
Sporotrichosis is a mycosis caused by fungi from the Sporothrix schenckii species complex, whose prototypical member is Sporothrix schenckii sensu stricto. Pattern recognition receptors (PRRs) recognize and respond to pathogen-associated molecular patterns (PAMPs) and shape the following adaptive immune response. A family of PRRs most frequently associated with fungal recognition is the nucleotide-binding oligomerization domain-like receptor (NLR). After PAMP recognition, NLR family pyrin domain-containing 3 (NLRP3) binds to apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 to form the NLRP3 inflammasome...
January 31, 2017: Immunology
https://www.readbyqxmd.com/read/28112808/nerve-growth-factor-a-neuroimmune-crosstalk-mediator-for-all-seasons
#14
REVIEW
Stephen D Skaper
Neurotrophic factors comprise a broad family of biomolecules - most of which are peptides or small proteins - that support the growth, survival, and differentiation of both developing and mature neurons. The prototypical example and best-characterized neurotrophic factor is nerve growth factor (NGF) which is widely recognized as a target-derived factor responsible for the survival and maintenance of the phenotype of specific subsets of peripheral neurons and basal forebrain cholinergic nuclei during development and maturation...
January 23, 2017: Immunology
https://www.readbyqxmd.com/read/28109007/retinoic-acid-inducible-gene-i-rig-i-like-receptors-rlrs-in-fish-current-knowledge-and-future-perspectives
#15
REVIEW
Shan Nan Chen, Peng Fei Zou, Pin Nie
Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are found conservatively present in teleost fish. All three members, RIG-I, MDA5 and LGP2 together with the downstream molecules such as MITA, TRAF3 and TBK1 have been identified in a range of fish species. However, it is a bit unexpected that RIG-I has not been reported in fish of Acanthopterygii, and it would be important to clarify the presence and role of RIG-I gene in a broad range of taxa in Teleostei. RLRs in fish can be induced in vivo and in vitro by viral pathogens as well as synthetic double-stranded RNA (dsRNA), poly(I:C), leading to the production of type I IFNs and the expression of IFN stimulated genes (ISGs)...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28108991/mucosal-immune-tolerance-at-the-ocular-surface-in-health-and-disease
#16
REVIEW
Jeremías G Galletti, Mauricio Guzmán, Mirta N Giordano
The ocular surface is constantly exposed to environmental irritants, allergens and pathogens, against which it can mount a prompt immune response to preserve its integrity. But to avoid unnecessary inflammation, the ocular surface's mucosal immune system must also discriminate between harmless and potentially dangerous antigens, a seemingly complicated task. Despite its unique features, the ocular surface is a mucosal lining, and as such, it shares some homeostatic and pathophysiological mechanisms with other mucosal surfaces...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28108989/tigit-signalling-pathway-negatively-regulates-cd4-t-cell-responses-in-systemic-lupus-erythematosus
#17
Lie Mao, Hongyan Hou, Shiji Wu, Yu Zhou, Juan Wang, Jing Yu, Xiaohui Wu, Yanfang Lu, Liyan Mao, Munyemana Jean Bosco, Feng Wang, Ziyong Sun
B-lymphocyte hyperactivity in systemic lupus erythematosus (SLE) is T-cell-dependent, and CD4(+) T-cell activation is essential to SLE pathogenesis. However, the mechanism of the deregulation of CD4(+) T cells in SLE is largely unknown. T-cell immunoglobulin and ITIM domain (TIGIT) is a new inhibitory receptor preferentially expressed on activated CD4(+) T cells. Here, we address the role of TIGIT in the pathogenesis of SLE. Our results showed that TIGIT expression on CD4(+) T cells was significantly elevated in patients with SLE and highly correlated with the activity of the disease...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28106253/massive-plasmablast-response-elicited-in-the-acute-phase-of-hantavirus-pulmonary-syndrome
#18
Marina García, Ayelén Iglesias, Verónica I Landoni, Carla Bellomo, Agostina Bruno, María Teresa Córdoba, Luciana Balboa, Gabriela C Fernández, María Del Carmen Sasiain, Valeria P Martínez, Pablo Schierloh
Beside its key diagnostic value, the humoral immune response is thought to play a protective role in hantavirus pulmonary syndrome. However, little is known about the cell source of these antibodies during ongoing human infection. Herein we characterized B-cell subsets circulating in Andes-virus-infected patients. A notable potent plasmablast (PB) response that increased 100-fold over the baseline levels was observed around 1 week after the onset of symptoms. These PB present a CD3(neg) CD19(low) CD20(neg) CD38(hi) CD27(hi) CD138(+/-) IgA(+/-) surface phenotype together with the presence of cytoplasmic functional immunoglobulins...
January 20, 2017: Immunology
https://www.readbyqxmd.com/read/28092402/%C3%AE-%C3%AE-t-cells-are-indispensable-for-interleukin-23-mediated-protection-against-concanavalin-a-induced-hepatitis-in-hepatitis-b-virus-transgenic-mice
#19
Ziyu Meng, Jingya Wang, Yifang Yuan, Guangchao Cao, Shuobing Fan, Chao Gao, Li Wang, Zheng Li, Xiaoli Wu, Zhenzhou Wu, Liqing Zhao, Zhinan Yin
Hepatitis B virus surface antigen (HBsAg) carriers are highly susceptible to liver injury triggered by environmental biochemical stimulation. Previously, we have reported an inverse correlation between γδ T cells and liver damage in patients with hepatitis B virus (HBV). However, whether γδ T cells play a role in regulating the hypersensitivity of HBsAg carriers to biochemical stimulation-induced hepatitis is unknown. In this study, using HBV transgenic (HBs-Tg) and HBs-Tg T-cell receptor-δ-deficient (TCR-δ(-/-) ) mice, we found that mice genetically deficient in γδ T cells exhibited more severe liver damage upon Concanavalin A (Con A) treatment, as indicated by substantially higher serum alanine aminotransferase levels, further elevated interferon-γ (IFN-γ) levels and more extensive necrosis...
January 16, 2017: Immunology
https://www.readbyqxmd.com/read/28066900/boosting-of-post-exposure-human-t-cell-and-b-cell-recall-responses-in-vivo-by-burkholderia-pseudomallei-related-proteins
#20
Arnone Nithichanon, Louise J Gourlay, Gregory J Bancroft, Manabu Ato, Yoshimasa Takahashi, Ganjana Lertmemongkolchai
Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease with high incidence and mortality in South East Asia and northern Australia. To date there is no protective vaccine and antibiotic treatment is prolonged and not always effective. Most people living in endemic areas have been exposed to the bacteria and have developed some immunity, which may have helped to prevent disease. Here, we used a humanized mouse model (hu-PBL-SCID), reconstituted with human peripheral blood mononuclear cells from seropositive donors, to illustrate the potential of three known antigens (FliC, OmpA and N-PilO2) for boosting both T-cell and B-cell immune responses...
January 9, 2017: Immunology
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