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https://www.readbyqxmd.com/read/29935219/cvid-patients-with-autoimmune-cytopenias-exhibit-hyperplastic-yet-inefficient-germinal-center-responses
#1
Neil Romberg, Carole Le Coz, Salomé Glauzy, Jean-Nicolas Schickel, Melissa Trofa, Brian E Nolan, Michele Paessler, Mina LuQing Xu, Michele Lambert, Saquib A Lakhani, Mustafa K Khokha, Soma Jyonouchi, Jennifer Heimall, Patricia Takach, Paul J Maglione, Jason Catanzaro, F Ida Hsu, Kathleen E Sullivan, Charlotte Cunningham-Rundles, Eric Meffre
BACKGROUND: The lack of pathogen-protective, isotype-switched antibodies in common variable immunodeficiency (CVID) suggests germinal center hypoplasia, yet a subset of CVID patients is paradoxically affected by autoantibody-mediated autoimmune cytopenias (AICs) and lymphadenopathy. OBJECTIVE: We sought to compare the physical characteristics and immunological output of germinal center responses in CVID patients with AICs (CVID+AIC) and without AICs (CVID-AICs)...
June 20, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29933397/human-tscm-cell-dynamics-in-vivo-are-compatible-with-long-lived-immunological-memory-and-stemness
#2
Pedro Costa Del Amo, Julio Lahoz Beneytez, Lies Boelen, Raya Ahmed, Kelly L Miners, Yan Zhang, Laureline Roger, Rhiannon E Jones, Silvia A Fuertes Marraco, Daniel E Speiser, Duncan M Baird, David A Price, Kristin Ladell, Derek Macallan, Becca Asquith
Adaptive immunity relies on the generation and maintenance of memory T cells to provide protection against repeated antigen exposure. It has been hypothesised that a self-renewing population of T cells, named stem cell-like memory T (TSCM) cells, are responsible for maintaining memory. However, it is not clear if the dynamics of TSCM cells in vivo are compatible with this hypothesis. To address this issue, we investigated the dynamics of TSCM cells under physiological conditions in humans in vivo using a multidisciplinary approach that combines mathematical modelling, stable isotope labelling, telomere length analysis, and cross-sectional data from vaccine recipients...
June 22, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29930723/dna-damage-predicts-prognosis-and-treatment-response-in-colorectal-liver-metastases-superior-to-immunogenic-cell-death-and-t-cells
#3
Johannes Laengle, Judith Stift, Agnes Bilecz, Brigitte Wolf, Andrea Beer, Balazs Hegedus, Stefan Stremitzer, Patrick Starlinger, Dietmar Tamandl, Dietmar Pils, Michael Bergmann
Preclinical models indicate that DNA damage induces type I interferon (IFN), which is crucial for the induction of an anti-tumor immune response. In human cancers, however, the association between DNA damage and an immunogenic cell death (ICD), including the release and sensing of danger signals, the subsequent ER stress response and a functional IFN system, is less clear. Methods: Neoadjuvant-treated colorectal liver metastases (CLM) patients, undergoing liver resection in with a curative intent, were retrospectively enrolled in this study (n=33)...
2018: Theranostics
https://www.readbyqxmd.com/read/29927676/developing-effective-vaccines-cues-from-natural-infection
#4
Vishakha Bhurani, Aditi Mohankrishnan, Alexandre Morrot, Sarat Kumar Dalai
The ultimate goal of any vaccine is to generate a heterogeneous and stable pool of memory lymphocytes. Vaccine are designed with the hope to generate antigen specific long-lived T cell responses, as it may be the case in natural infection; however, inducing such response by sub-unit vaccine has been a challenge. Although significant progress has been made, there is lot of scope for designing novel vaccine strategies by taking cues from the natural infection. This review focuses upon the roadblocks and the possible ways to overcome them leading to developing effective vaccines...
June 21, 2018: International Reviews of Immunology
https://www.readbyqxmd.com/read/29926732/influence-of-biological-sex-age-and-hiv-status-in-an-in-vitro-primary-cell-model-of-hiv-latency-using-a-cxcr4-tropic-virus
#5
Amanda B Macedo, Rachel S Resop, Laura Jean Martins, Matthew A Szaniawski, Eric S Sorensen, Adam M Spivak, Douglas F Nixon, R Brad Jones, Vicente Planelles, Alberto Bosque
Primary cell models of HIV latency have become tools to both understand the mechanisms involved in the establishment of latency as well as to test pre-clinical strategies towards an HIV-1 cure. These models rely on the infection of CD4 T cells from healthy donors. As such, these models provide an opportunity to explore the role of biological sex, age and HIV status on the establishment and reactivation of latent HIV in vitro. We have used an established primary cell model of latency based on the generation of latently infected central memory CD4 T cells with the CXCR4-strain HIV-1NL4-3 to address whether these variables influence: i) HIV-1NL4-3 replication, ii) establishment of latency, and iii) latency reversal in CD4 T cells...
June 21, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29925906/antibodies-conjugated-with-viral-antigens-elicit-a-cytotoxic-t-cell-response-against-primary-cll-ex-vivo
#6
Viktor Schneidt, Marta Ilecka, Peter Dreger, Dwain G van Zyl, Susanne Fink, Josef Mautner, Henri-Jacques Delecluse
Chronic lymphocytic leukemia (CLL) is the most frequent B cell malignancy in Caucasian adults. The therapeutic armamentarium against this incurable disease has recently seen a tremendous expansion with the introduction of specific pathway inhibitors and innovative immunotherapy. However, none of these approaches is curative and devoid of side effects. We have used B-cell-specific antibodies conjugated with antigens (AgAbs) of the Epstein-Barr virus (EBV) to efficiently expand memory CD4+ cytotoxic T lymphocytes (CTLs) that recognized viral epitopes in 12 treatment-naive patients with CLL...
June 20, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29925891/targeting-the-association-between-telomere-length-and-immuno-cellular-bioenergetics-in-female-patients-with-major-depressive-disorder
#7
Christina Boeck, Juan Salinas-Manrique, Enrico Calzia, Peter Radermacher, Christine A F von Arnim, Detlef E Dietrich, Iris-Tatjana Kolassa, Alexander Karabatsiakis
Major Depressive Disorder (MDD) has been associated with telomere dysfunction and alterations in mitochondrial activity, which seem to be co-regulated in human cells. To investigate this co-regulation in MDD, we assessed telomere length (TL) in peripheral blood mononuclear cells (PBMC) and selected immune cell subsets by quantitative fluorescence in situ hybridization and mitochondrial respiratory activity in PBMC by high-resolution respirometry in a study cohort of 18 MDD patients and 21 non-depressed controls...
June 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29925664/prolonged-evolution-of-virus-specific-memory-t-cell-immunity-post-severe-avian-influenza-a-h7n9-virus-infection
#8
Min Zhao, Junbo Chen, Shuguang Tan, Tao Dong, Hui Jiang, Jiandong Zheng, Chuansong Quan, Qiaohong Liao, Hangjie Zhang, Xiling Wang, Qianli Wang, Yuhai Bi, Fengfeng Liu, Luzhao Feng, Peter W Horby, Paul Klenerman, George F Gao, William J Liu, Hongjie Yu
Since 2013, influenza A/H7N9 has emerged as the commonest avian influenza subtype causing human infection, and is associated with a high fatality risk. However, the characteristics of immune memory in patients who have recovered from H7N9 infection are not well understood. We assembled a cohort of forty-five H7N9 survivors followed for up to 15 months after infection. Humoral and cellular immune responses were analyzed in sequential samples obtained at 1.5-4 months, 6-8 months and 12-15 months post-infection...
June 20, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29924995/age-related-decline-in-primary-cd8-t-cell-responses-is-associated-with-the-development-of-senescence-in-virtual-memory-cd8-t-cells
#9
Kylie M Quinn, Annette Fox, Kim L Harland, Brendan E Russ, Jasmine Li, Thi H O Nguyen, Liyen Loh, Moshe Olshanksy, Haroon Naeem, Kirill Tsyganov, Florian Wiede, Rosela Webster, Chantelle Blyth, Xavier Y X Sng, Tony Tiganis, David Powell, Peter C Doherty, Stephen J Turner, Katherine Kedzierska, Nicole L La Gruta
Age-associated decreases in primary CD8+ T cell responses occur, in part, due to direct effects on naive CD8+ T cells to reduce intrinsic functionality, but the precise nature of this defect remains undefined. Aging also causes accumulation of antigen-naive but semi-differentiated "virtual memory" (TVM ) cells, but their contribution to age-related functional decline is unclear. Here, we show that TVM cells are poorly proliferative in aged mice and humans, despite being highly proliferative in young individuals, while conventional naive T cells (TN cells) retain proliferative capacity in both aged mice and humans...
June 19, 2018: Cell Reports
https://www.readbyqxmd.com/read/29924976/innate-lymphoid-cells-diversity-plasticity-and-unique-functions-in-immunity
#10
REVIEW
Marco Colonna
Type 1, 2, and 3 innate lymphoid cells (ILCs) have emerged as tissue-resident innate correlates of T helper 1 (Th1), Th2, and Th17 cells. Recent studies suggest that ILCs are more diverse than originally proposed; this might reflect truly distinct lineages or adaptation of ILCs to disparate tissue microenvironments, known as plasticity. Given that ILCs strikingly resemble T cells, are they redundant? While the regulation, timing, and magnitude of ILC and primary T cell responses differ, tissue-resident memory T cells may render ILCs redundant during secondary responses...
June 19, 2018: Immunity
https://www.readbyqxmd.com/read/29924875/in-silico-and-ex-vivo-approaches-indicate-immune-pressure-on-capsid-and-non-capsid-regions-of-coxsackie-b-viruses-in-the-human-system
#11
Rhiannon Kundu, Robin Knight, Meenakshi Dunga, Mark Peakman
Coxsackie B Virus (CBV) infection has been linked to the aetiology of type 1 diabetes (T1D) and vaccination has been proposed as prophylaxis for disease prevention. Serum neutralising antibodies and the presence of viral protein and RNA in tissues have been common tools to examine this potential disease relationship, whilst the role of anti-CBV cytotoxic T cell responses and their targets have not been studied. To address this knowledge gap, we augmented conventional HLA-binding predictive algorithm-based epitope discovery by cross-referencing epitopes with sites of positive natural selection within the CBV3 viral genome, identified using mixed effects models of evolution...
2018: PloS One
https://www.readbyqxmd.com/read/29924317/association-between-immunosenescence-phenotypes-and-pre-frailty-in-older-subjects-does-cytomegalovirus-play-a-role
#12
Hung Cao Dinh, Ivan Bautmans, Ingo Beyer, Tony Mets, Oscar Okwudiri Onyema, Louis Nuvagah Forti, Wim Renmans, Sam Vander Meeren, Kristin Jochmans, Sofie Vermeiren, Roberta Vella Azzopardi, Rose Njemini
Frailty is highly prevalent in old age and confers an important mortality risk. Although the causes of frailty are multiple, immuno-senescence (IS) - predominantly driven by cytomegalovirus (CMV) - has been implicated in its pathophysiology. Thus far, research examining the association between IS and frailty states is sparse and equivocal. On the other hand, evidence is mounting in support of the view that frailty can be reversed, especially for those in the pre-frail stage. Therefore, we aimed to clarify the impact of CMV on IS and its relevance to pre-frailty...
June 19, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29923437/effect-of-cyclophosphamide-treatment-on-central-and-effector-memory-t-cells-in-mice
#13
Marcin Włodarczyk, Elżbieta Ograczyk, Magdalena Kowalewicz-Kulbat, Magdalena Druszczyńska, Wiesława Rudnicka, Marek Fol
Immunological memory is a key feature of adaptive immunity. It provides the organism with long-lived and robust protection against infection. The important question is whether cyclophosphamide (CP), as immunosuppressive agent used in cancer therapy and in some autoimmune diseases, may act on the memory T-cell population. We investigated the effect of CP on the percentage of central memory T cells (TCM ) and effector memory T cells (TEM ) in the mouse model of CP-induced immunosuppression (8-10-week-old male C57BL/6 mice CP treated for 7 days at the daily dose of 50 μg/g body weight [bw], manifested the best immunosuppression status, as compared to lower doses of CP: 10 or 20 μg/g bw)...
January 1, 2018: International Journal of Toxicology
https://www.readbyqxmd.com/read/29923026/inhibition-of-the-adenosine-a2a-receptor-modulates-expression-of-t-cell-coinhibitory-receptors-and-improves-effector-function-for-enhanced-checkpoint-blockade-and-act-in-murine-cancer-models
#14
Robert D Leone, Im-Meng Sun, Min-Hee Oh, Im-Hong Sun, Jiayu Wen, Judson Englert, Jonathan D Powell
Adenosine signaling via the A2a receptor (A2aR) is emerging as an important checkpoint of immune responses. The presence of adenosine in the inflammatory milieu or generated by the CD39/CD73 axis on tissues or T regulatory cells serves to regulate immune responses. By nature of the specialized metabolism of cancer cells, adenosine levels are increased in the tumor microenvironment and contribute to tumor immune evasion. To this end, small molecule inhibitors of the A2aR are being pursued clinically to enhance immunotherapy...
June 19, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29922298/t-cell-receptor-major-histocompatibility-complex-interaction-strength-defines-trafficking-and-cd103-memory-status-of-cd8-t-cells-in-the-brain
#15
Anna Sanecka, Nagisa Yoshida, Elizabeth Motunrayo Kolawole, Harshil Patel, Brian D Evavold, Eva-Maria Frickel
T cell receptor-major histocompatibility complex (TCR-MHC) affinities span a wide range in a polyclonal T cell response, yet it is undefined how affinity shapes long-term properties of CD8 T cells during chronic infection with persistent antigen. Here, we investigate how the affinity of the TCR-MHC interaction shapes the phenotype of memory CD8 T cells in the chronically Toxoplasma gondii- infected brain. We employed CD8 T cells from three lines of transnuclear (TN) mice that harbor in their endogenous loci different T cell receptors specific for the same Toxoplasma antigenic epitope ROP7...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29920369/scrutinizing-mycobacterium-tuberculosis-membrane-and-secretory-proteins-to-formulate-multiepitope-subunit-vaccine-against-pulmonary-tuberculosis-by-utilizing-immunoinformatic-approaches
#16
Nina Chatterjee, Rupal Ojha, Nazia Khatoon, Vijay Kumar Prajapati
Tuberculosis is a menacing disease caused eminently to the people inhabiting the tropical and sub-tropical nations. A holistic approach is required to generate T and B memory cells to effectuate a long-term exemption from the pulmonary tuberculosis. In this study, immunoinformatic approaches were used to design a multi-epitope-based subunit vaccine for pulmonary tuberculosis which may improve human immune system. The various B-cell, TH cell and TC cell binding epitopes were predicted for selected 2 membrane and 12 secretory proteins of Mycobacterium tuberculosis...
June 16, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29920186/th1-th17-polarization-persists-following-whole-cell-pertussis-vaccination-despite-repeated-acellular-boosters
#17
Ricardo da Silva Antunes, Mariana Babor, Chelsea Carpenter, Natalie Khalil, Mario Cortese, Alexander J Mentzer, Grégory Seumois, Christopher D Petro, Lisa A Purcell, Pandurangan Vijayanand, Shane Crotty, Bali Pulendran, Bjorn Peters, Alessandro Sette
In the mid-1990s, whole-cell (wP) pertussis vaccines were associated with local and systemic adverse events, which prompted their replacement with acellular (aP) vaccines in many high-income countries. In the past decade rates of pertussis disease have increased in children receiving only acellular pertussis vaccines. We compared the immune responses to acellular pertussis boosters in children who received their initial doses with either wP or aP vaccines using activation-induced marker (AIM) assays. Specifically, we examined pertussis-specific memory CD4+ T cell responses ex vivo, highlighting a Type 2/Th2 versus Type 1/Th1 and Th17 differential polarization as a function of childhood vaccination...
June 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29915585/signal-transducer-and-activator-of-transcription-3-hyperactivation-associates-with-follicular-helper-t-cell-differentiation-and-disease-activity-in-rheumatoid-arthritis
#18
Jun Deng, Chaofan Fan, Xin Gao, Qunxiong Zeng, Ruru Guo, Yunbo Wei, Zhian Chen, Yanan Chen, Dongcheng Gong, Jia Feng, Yan Xia, Shifei Xiang, Shushi Gong, Lin Yuan, Wei Shen, Wenyan Shen, Lin Lin, Ting Jiang, Dongyi He, Liangjing Lu, Xiaoxiang Chen, Di Yu
Follicular helper T (Tfh) cells are the specialized CD4+ T cell subset that supports B cells to produce high-affinity antibodies and generate humoral memory. Not only is the function of Tfh cells instrumental to mount protect antibodies but also to support autoantibody production and promote systemic inflammation in autoimmune diseases. However, it remains unclear how the activation of Tfh cells is driven in autoimmune diseases. Here, we report that in patients with rheumatoid arthritis (RA), excessive generation of CXCR5+ PD-1+ memory Tfh cells was observed and the frequency of memory Tfh cells correlated with disease activity score calculator for RA (DAS28)...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29915583/mass-cytometry-analysis-reveals-the-landscape-and-dynamics-of-cd32a-cd4-t-cells-from-early-hiv-infection-to-effective-cart
#19
Sixtine Coindre, Nicolas Tchitchek, Lamine Alaoui, Bruno Vaslin, Christine Bourgeois, Cecile Goujard, Veronique Avettand-Fenoel, Camille Lecuroux, Pierre Bruhns, Roger Le Grand, Anne-Sophie Beignon, Olivier Lambotte, Benoit Favier
CD32a has been proposed as a specific marker of latently HIV-infected CD4+ T cells. However, CD32a was recently found to be expressed on CD4+ T cells of healthy donors, leading to controversy on the relevance of this marker in HIV persistence. Here, we used mass cytometry to characterize the landscape and variation in the abundance of CD32a+ CD4+ T cells during HIV infection. To this end, we analyzed CD32a+ CD4+ T cells in primary HIV infection before and after effective combination antiretroviral therapy (cART) and in healthy donors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29915577/centrin-deleted-leishmania-donovani-parasites-help-cd4-t-cells-to-acquire-th1-phenotype-and-multi-functionality-through-downregulation-of-cd200-cd200r-immune-inhibitory-axis
#20
Rakesh K Singh, Sreenivas Gannavaram, Nevien Ismail, Amit Kaul, Mallikarjuna Rao Gedda, Hira L Nakhasi
The protozoan parasite Leishmania has evolved several strategies to undermine host defense mechanisms by inducing Th2-type adaptive immunity and suppressing effector functions of Th1 phenotype. In our earlier studies, using centrin gene-deleted Leishmania (LdCen-/- ) parasites as an immunogen, we have shown induction of an effective Th1-type immunity and robust memory responses that mediate protection against virulent challenge. However, role of inhibitory signals in Leishmania vaccine induced immunity in general, and LdCen-/- in particular has not been studied...
2018: Frontiers in Immunology
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