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https://www.readbyqxmd.com/read/28099084/mechanisms-and-new-strategies-for-primary-sj%C3%A3-gren-s-syndrome
#1
Clio P Mavragani
Primary Sjögren's syndrome (SS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, mainly salivary and lacrimal, resulting in oral and ocular dryness, although virtually any organ system can be affected. SS-related systemic manifestations are classified as either related to the presence of periepithelial infiltrates in exocrine and parenchymal organs or resulting from immunocomplex deposition due to B cell hyperactivity with increased risk for B cell lymphoma development...
January 14, 2017: Annual Review of Medicine
https://www.readbyqxmd.com/read/28097811/fc-silent-anti-cd154-domain-antibody-effectively-prevents-non-human-primate-renal-allograft-rejection
#2
Steven C Kim, Walter Wakwe, Laura B Higginbotham, David V Mathews, Cynthia P Breeden, Allison C Stephenson, Joe Jenkins, Elizabeth Strobert, Karen Price, Laura Price, Robert Kuhn, Haiqing Wang, Aaron Yamniuk, Suzanne Suchard, Alton B Farris, Thomas C Pearson, Christian P Larsen, Mandy L Ford, Anish Suri, Steven Nadler, Andrew B Adams
The advent of costimulation blockade provides the prospect for targeted therapy with improved graft survival in transplant patients. Perhaps the most effective costimulation blockade in experimental models is the use of reagents to block the CD40/CD154 pathway. Unfortunately, successful clinical translation of anti-CD154 therapy has not been achieved. In an attempt to develop an agent that is as effective as previous CD154 blocking antibodies but lacks the risk of thromboembolism, we evaluated the efficacy and safety of a novel anti-human CD154 domain antibody (dAb, BMS-986004)...
January 17, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28094276/b7-h3-participates-in-the-development-of-asthma-by-augmentation-of-the-inflammatory-response-independent-of-tlr2-pathway
#3
Wenjing Gu, Xinxing Zhang, Yongdong Yan, Yuqing Wang, Li Huang, Meijuan Wang, Xuejun Shao, Zhengrong Chen, Wei Ji
B7-H3, a new member of the B7 superfamily, acts as both a T cell costimulator and coinhibitor. Recent studies identified B7-H3 plays a critical role in the development of asthma. But the definitive mechanism is not clear. In this study, we further report that B7-H3 participates in the development of OVA-induced asthma in a murine model. And study its mechanism through the vitro and vivo experiment. Exogenous administration of B7-H3 strongly amplified the inflammatory response and augmented proinflammatory cytokines in vitro and vivo...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28092486/use-of-polyclonal-monoclonal-antibody-therapies-in-transplantation
#4
Melissa Y Yeung, Steven Gabardi, Mohamed H Sayegh
For over thirty years, antibody (mAb)-based therapies have been a standard component of transplant immunosuppression, and yet much remains to be learned in order for us to truly harness their therapeutic capabilities. Current mAbs used in transplant directly target and destroy graft-destructive immune cells, interrupt cytokine and costimulation-dependent T and B cell activation, and prevent down-stream complement activation. Areas covered: This review summarizes our current approaches to using antibody-based therapies to prevent and treat allograft rejection...
January 16, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28077684/targeting-aurora-kinase-a-and-jak2-prevents-gvhd-while-maintaining-treg-and-antitumor-ctl-function
#5
Brian C Betts, Anandharaman Veerapathran, Joseph Pidala, Hua Yang, Pedro Horna, Kelly Walton, Christopher L Cubitt, Steven Gunawan, Harshani R Lawrence, Nicholas J Lawrence, Said M Sebti, Claudio Anasetti
Graft-versus-host disease (GVHD) is a leading cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation. T cell costimulation by CD28 contributes to GVHD, but prevention is incomplete when targeting CD28, downstream mammalian target of rapamycin (mTOR), or Aurora A. Likewise, interleukin-6 (IL-6)-mediated Janus kinase 2 (JAK2) signaling promotes alloreactivity, yet JAK2 inhibition does not eliminate GVHD. We provide evidence that blocking Aurora A and JAK2 in human T cells is synergistic in vitro, prevents xenogeneic GVHD, and maintains antitumor responses by cytotoxic T lymphocytes (CTLs)...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28067900/donor-cd19-car-t-cells-exert-potent-graft-versus-lymphoma-activity-with-diminished-graft-versus-host-activity
#6
Arnab Ghosh, Melody Smith, Scott E James, Marco L Davila, Enrico Velardi, Kimon V Argyropoulos, Gertrude Gunset, Fabiana Perna, Fabiana M Kreines, Emily R Levy, Sophie Lieberman, Hillary V Jay, Andrea Z Tuckett, Johannes L Zakrzewski, Lisa Tan, Lauren F Young, Kate Takvorian, Jarrod A Dudakov, Robert R Jenq, Alan M Hanash, Ana Carolina F Motta, George F Murphy, Chen Liu, Andrea Schietinger, Michel Sadelain, Marcel R M van den Brink
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for hematological malignancies. However, graft-versus-host disease (GVHD) and relapse after allo-HSCT remain major impediments to the success of allo-HSCT. Chimeric antigen receptors (CARs) direct tumor cell recognition of adoptively transferred T cells. CD19 is an attractive CAR target, which is expressed in most B cell malignancies, as well as in healthy B cells. Clinical trials using autologous CD19-targeted T cells have shown remarkable promise in various B cell malignancies...
January 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28031339/staphylococcus-aureus-protein-a-disrupts-immunity-mediated-by-long-lived-plasma-cells
#7
Amanda B Keener, Lance T Thurlow, SunAh Kang, Nicholas A Spidale, Stephen H Clarke, Kenji M Cunnion, Roland Tisch, Anthony R Richardson, Barbara J Vilen
Infection with Staphylococcus aureus does not induce long-lived protective immunity for reasons that are not completely understood. Human and murine vaccine studies support a role for Abs in protecting against recurring infections, but S. aureus modulates the B cell response through expression of staphylococcus protein A (SpA), a surface protein that drives polyclonal B cell expansion and induces cell death in the absence of costimulation. In this murine study, we show that SpA altered the fate of plasmablasts and plasma cells (PCs) by enhancing the short-lived extrafollicular response and reducing the pool of bone marrow (BM)-resident long-lived PCs...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28026044/expression-of-programmed-cell-death-1-and-its-ligand-b7-homolog-1-in-peripheral-blood-lymphocytes-from-patients-with-peripartum-cardiomyopathy
#8
Guozhi Xia, Xiaopu Zheng, Xinye Yao, Xiaowei Yao, Zhongwei Liu, Junkui Wang
BACKGROUND: Immune response has been postulated to play a prominent role in the pathogenesis of peripartum cardiomyopathy (PPCM). Given the importance of programmed death (PD)-1 and its ligand B7 homologue 1 (B7-H1) costimulatory molecules as an immune regulatory pathway, this study aimed to investigate the effect of PD-1 and B7-H1 expression on immune response in peripheral blood lymphocytes from the patients with PPCM. HYPOTHESIS: PD-1 and B7-H1 may be involved in modulating immune response in PPCM...
December 27, 2016: Clinical Cardiology
https://www.readbyqxmd.com/read/28018354/impact-of-the-mica-129met-val-dimorphism-on-nkg2d-mediated-biological-functions-and-disease-risks
#9
REVIEW
Antje Isernhagen, Dörthe Malzahn, Heike Bickeböller, Ralf Dressel
The major histocompatibility complex (MHC) class I chain-related A (MICA) is the most polymorphic non-classical MHC class I gene in humans. It encodes a ligand for NKG2D (NK group 2, member D), an activating natural killer (NK) receptor that is expressed mainly on NK cells and CD8(+) T cells. The single-nucleotide polymorphism (SNP) rs1051792 causing a valine (Val) to methionine (Met) exchange at position 129 of the MICA protein is of specific interest. It separates MICA into isoforms that bind NKG2D with high (Met) and low affinities (Val)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28009481/renal-allograft-survival-in-nonhuman-primates-infused-with-donor-antigen-pulsed-autologous-regulatory-dendritic-cells
#10
M B Ezzelarab, D Raich-Regue, L Lu, A F Zahorchak, A Perez-Gutierrez, A Humar, M Wijkstrom, M Minervini, R W Wiseman, D K C Cooper, A E Morelli, A W Thomson
Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg pre-loaded with cell membrane vesicles from allogeneic PBMC, induce T cell hyporesponsiveness to donor alloAg in vitro. These donor alloAg-pulsed autologous DCreg (1.4-3.6 x 10(6) /kg) were administered intravenously, one day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 [CTLA4] Ig) and tapered rapamycin...
December 23, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28008916/fas-cd95-prevents-autoimmunity-independently-of-lipid-raft-localization-and-efficient-apoptosis-induction
#11
Anthony C Cruz, Madhu Ramaswamy, Claudia Ouyang, Christopher A Klebanoff, Prabuddha Sengupta, Tori N Yamamoto, Françoise Meylan, Stacy K Thomas, Nathan Richoz, Robert Eil, Susan Price, Rafael Casellas, V Koneti Rao, Jennifer Lippincott-Schwartz, Nicholas P Restifo, Richard M Siegel
Mutations affecting the apoptosis-inducing function of the Fas/CD95 TNF-family receptor result in autoimmune and lymphoproliferative disease. However, Fas can also costimulate T-cell activation and promote tumour cell growth and metastasis. Palmitoylation at a membrane proximal cysteine residue enables Fas to localize to lipid raft microdomains and induce apoptosis in cell lines. Here, we show that a palmitoylation-defective Fas C194V mutant is defective in inducing apoptosis in primary mouse T cells, B cells and dendritic cells, while retaining the ability to enhance naive T-cell differentiation...
December 23, 2016: Nature Communications
https://www.readbyqxmd.com/read/28008806/role-of-il-26-cd26-cd4-t-cells-in-pulmonary-chronic-graft-versus-host-disease-and-treatment-with-caveolin-1-ig-fc-conjugate
#12
Kei Ohnuma, Ryo Hatano, Takumi Itoh, Noriaki Iwao, Nam H Dang, Chikao Morimoto
Obliterative bronchiolitis is the primary noninfectious pulmonary complication after allogeneic hematopoietic cell transplantation and the only pathognomonic manifestation of pulmonary chronic graft-versus-host disease (cGVHD). In our recent study, we identified a novel effect of IL-26, which is absent in rodents, on transplant related-obliterative bronchiolitis. Sublethally irradiated NOD/Shi-scidIL2rγnull mice transplanted with human umbilical cord blood gradually exhibited obliterative bronchiolitis with increased collagen deposition and predominant infiltration with human IL-26+CD26+CD4 T cells...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/28000531/cytokines-and-metabolic-factors-regulate-tumoricidal-t-cell-function-during-cancer-immunotherapy
#13
Adam J Adler, Payal Mittal, Joseph M Ryan, Beiyan Zhou, Jeffrey S Wasser, Anthony T Vella
Recent advances in cancer biology and genetics have fostered precision therapies targeting tumor-specific attributes. Immune-based therapies that elicit cytolytic T cells (CTL) specific for tumor antigens can provide therapeutic benefit to cancer patients, however, cure rates are typically low. This largely results from immunosuppressive mechanisms operating within the tumor microenvironment, many of which inflict metabolic stresses upon CTL. Conversely, immunotherapies can mitigate specific metabolic stressors...
January 2017: Immunotherapy
https://www.readbyqxmd.com/read/27987496/-detection-of-peripheral-follicular-helper-t-cells-in-rheumatoid-arthritis
#14
L M An, J Li, L L Ji, G T Li, Z L Zhang
OBJECTIVE: To detect cell frequency and surface markers of peripheral CD4(+)CXCR5+ follicular helper T (Tfh) cells and analyze the correlation between CD4(+)CXCR5(+)Tfh cells and rheumatoid arthritis (RA) disease activity. METHODS: Forty RA patients meeting the American College of Rheumatology classification criteria for RA and twenty healthy controls (HC) were included. The peripheral blood mononuclear cells and sera were collected. The expressions of CD4+CXCR5(+)Tfh cells (CXCR5, C-X-C chemokine receptor type 5) and inducible T cell costimulator (ICOS), programmed death 1 positive (PD-1), interleukin-21 receptor (IL-21R) and CD40 ligand (CD40L) positive on CD4(+)CXCR5(+)Tfh cells were analyzed by flow cytometry...
December 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/27965674/molecular-and-cellular-characterization-of-human-cd8-t-suppressor-cells
#15
REVIEW
Zheng Xu, Sophey Ho, Chih-Chao Chang, Qing-Yin Zhang, Elena-Rodica Vasilescu, George Vlad, Nicole Suciu-Foca
Bidirectional interactions between dendritic cells and Ag-experienced T cells initiate either a tolerogenic or immunogenic pathway. The outcome of these interactions is of crucial importance in malignancy, transplantation, and autoimmune diseases. Blockade of costimulation results in the induction of T helper cell anergy and subsequent differentiation of antigen-specific CD8(+) T suppressor/regulatory cells (Ts). Ts, primed in the presence of inhibitory signals, exert their inhibitory function in an antigen-specific manner, a feature with tremendous clinical potential...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27941004/optimization-of-peptide-vaccines-to-induce-robust-antitumor-cd4-t-cell-responses
#16
Takumi Kumai, Sujin Lee, Hyun-Il Cho, Hussein Sultan, Hiroya Kobayashi, Yasuaki Harabuchi, Esteban Celis
Substantial evidence indicates that immunotherapy is a feasible and effective approach for the treatment of numerous types of cancer. Among various immunotherapy options, peptide vaccines to generate antitumor T cells appear as promising candidates, because of their cost effectiveness and ease of implementation. Nevertheless, most peptide vaccines are notorious for being weekly immunogenic and, thus, optimization of the vaccination strategy is essential to achieve therapeutic effectiveness. In addition, effective peptide vaccines must stimulate both CD8 cytotoxic and CD4 helper T lymphocytes...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27931292/circulating-follicular-t-helper-cell-subset-distribution-in-patients-with-asthma
#17
Fang Gong, Chunyan Qian, HuaYan Zhu, Jie Zhu, Yuhong Pan, QiaoJing Dong, DongLin Jiang
BACKGROUND: The pathogenesis of allergic asthma is primarily characterized by abnormality in the immunoglobulin E (IgE) pathway, suggesting a possible role for follicular T-helper cells (Tfh) in the genesis of excessive IgE accumulation. The blood chemokine (C-X-C motif) receptor 5 (CXCR5)+CD4+ T cells, known as circulating Tfh, share common functional characteristics with Tfh cells from germinal centers. There are three subsets of circulating Tfh cells: Tfh1 (CXCR3+CC chemokine receptor [CCR] 6), Tfh2 (CXCR3CCR6) and Tfh17 (CXCR3CCR6+)...
November 2016: Allergy and Asthma Proceedings:
https://www.readbyqxmd.com/read/27928019/tlr2-ligation-enhances-hiv-1-replication-in-activated-ccr6-cd4-t-cells-by-increasing-virus-entry-and-establishing-a-more-permissive-environment-to-infection
#18
Jean-François Bolduc, Michel Ouellet, Laurent Hany, Michel J Tremblay
: In this study, we investigated the effect of TLR2 ligation on the permissiveness of activated CD4(+) T cells to HIV-1 infection by focusing our experiments on the relative susceptibility of cell subsets based on their expression of CCR6. Purified primary human CD4(+) T cells were first subjected to a CD3/CD28 costimulation before treatment with the TLR2 agonist Pam3CSK4. Finally, cells were inoculated with R5-tropic HIV-1 particles that permit to study the effect of TLR2 triggering on virus production at both population and single-cell levels...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27926546/the-effect-of-chronic-kidney-disease-on-t-cell-alloimmunity
#19
Pamela D Winterberg, Mandy L Ford
PURPOSE OF REVIEW: Altered differentiation and activation of T-cell subsets occur in patients with chronic kidney disease (CKD), but the impact on graft rejection and protective immunity during transplantation are not fully understood. RECENT FINDINGS: Patients with CKD have decreased frequency of naïve T cells, accumulation of activated, terminally differentiated memory cells, and skewed regulatory versus T helper 17 ratio. Naïve and memory T-cell subsets do not appear to improve following kidney transplantation...
February 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27923915/late-phase-synthesis-of-i%C3%AE%C2%BAb%C3%AE-insulates-the-tlr4-activated-canonical-nf-%C3%AE%C2%BAb-pathway-from-noncanonical-nf-%C3%AE%C2%BAb-signaling-in-macrophages
#20
Budhaditya Chatterjee, Balaji Banoth, Tapas Mukherjee, Nandaraj Taye, Bharath Vijayaragavan, Samit Chattopadhyay, James Gomes, Soumen Basak
The nuclear factor κB (NF-κB) transcription factors coordinate the inflammatory immune response during microbial infection. Pathogenic substances engage canonical NF-κB signaling through the heterodimer RelA:p50, which is subjected to rapid negative feedback by inhibitor of κBα (IκBα). The noncanonical NF-κB pathway is required for the differentiation of immune cells; however, cross-talk between both pathways can occur. Concomitantly activated noncanonical signaling generates p52 from the p100 precursor...
December 6, 2016: Science Signaling
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