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self reactive T cell

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https://www.readbyqxmd.com/read/28202751/superiority-in-rhesus-macaques-of-targeting-hiv-1-env-gp140-to-cd40-versus-lox-1-in-combination-with-replication-competent-nyvac-kc-for-induction-of-env-specific-antibody-and-t-cell-responses
#1
Gerard Zurawski, Xiaoying Shen, Sandra Zurawski, Georgia D Tomaras, David C Montefiori, Mario Roederer, Guido Ferrari, Christine Lacabaratz, Peter Klucar, Zhiqing Wang, Kathryn E Foulds, Shing-Fen Kao, Xuesong Yu, Alicia Sato, Nicole L Yates, Celia LaBranche, Sherry Stanfield-Oakley, Karen Kibler, Bertram Jacobs, Andres Salazar, Steve Self, Jimmy Fulp, Raphael Gottardo, Lindsey Galmin, Deborah Weiss, Anthony Cristillo, Giuseppe Pantaleo, Yves Levy
We compared the HIV-1-specific immune responses generated by targeting HIV-1 envelope protein (Env gp140) to either CD40 or LOX-1, two endocytic receptors on dendritic cells (DCs), in Rhesus macaques primed with a poxvirus vector (NYVAC-KC) expressing Env gp140. The DC-targeting vaccines, humanized recombinant monoclonal antibodies fused to Env gp140, were administered as a boost with poly ICLC adjuvant either alone or co-administered with the NYVAC-KC vector. All the DC-targeting vaccine administrations with poly ICLC increased the low-level serum anti-Env IgG responses elicited by NYVAC-KC priming significantly more (up to P =0...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28202731/microfluidic-droplet-platform-for-ultrahigh-throughput-single-cell-screening-of-biodiversity
#2
Stanislav S Terekhov, Ivan V Smirnov, Anastasiya V Stepanova, Tatyana V Bobik, Yuliana A Mokrushina, Natalia A Ponomarenko, Alexey A Belogurov, Maria P Rubtsova, Olga V Kartseva, Marina O Gomzikova, Alexey A Moskovtsev, Anton S Bukatin, Michael V Dubina, Elena S Kostryukova, Vladislav V Babenko, Maria T Vakhitova, Alexander I Manolov, Maja V Malakhova, Maria A Kornienko, Alexander V Tyakht, Anna A Vanyushkina, Elena N Ilina, Patrick Masson, Alexander G Gabibov, Sidney Altman
Ultrahigh-throughput screening (uHTS) techniques can identify unique functionality from millions of variants. To mimic the natural selection mechanisms that occur by compartmentalization in vivo, we developed a technique based on single-cell encapsulation in droplets of a monodisperse microfluidic double water-in-oil-in-water emulsion (MDE). Biocompatible MDE enables in-droplet cultivation of different living species. The combination of droplet-generating machinery with FACS followed by next-generation sequencing and liquid chromatography-mass spectrometry analysis of the secretomes of encapsulated organisms yielded detailed genotype/phenotype descriptions...
February 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28195200/dynamical-footprint-of-cross-reactivity-in-a-human-autoimmune-t-cell-receptor
#3
Amit Kumar, Francesco Delogu
The present work focuses on the dynamical aspects of cross-reactivity between myelin based protein (MBP) self-peptide and two microbial peptides (UL15, PMM) for Hy.1B11 T-cell receptor (TCR). This same TCR was isolated from a patient suffering from multiple sclerosis (MS). The study aims at highlighting the chemical interactions underlying recognition mechanisms between TCR and the peptides presented by Major Histocompatibility Complex (MHC) proteins, which form a crucial component in adaptive immune response against foreign antigens...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28164137/immune-responses-to-tissue-restricted-nonmajor-histocompatibility-complex-antigens-in-allograft-rejection
#4
REVIEW
Ankit Bharat, T Mohanakumar
Chronic diseases that result in end-stage organ damage cause inflammation, which can reveal sequestered self-antigens (SAgs) in that organ and trigger autoimmunity. The thymus gland deletes self-reactive T-cells against ubiquitously expressed SAgs, while regulatory mechanisms in the periphery control immune responses to tissue-restricted SAgs. It is now established that T-cells reactive to SAgs present in certain organs (e.g., lungs, pancreas, and intestine) are incompletely eliminated, and the dysregulation of peripheral immuneregulation can generate immune responses to SAgs...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28157168/regulation-of-t-cell-activation-and-differentiation-by-extracellular-vesicles-and-their-pathogenic-role-in-systemic-lupus-erythematosus-and-multiple-sclerosis
#5
REVIEW
Cristina Ulivieri, Cosima T Baldari
How autoreactive tissue-infiltrated effector T cells are induced and sustained in autoimmune disease, usually dominated by the Th1 and Th17 subsets, is still largely unknown. In organ-specific autoimmunity, self-reactive T cells initially activated by dendritic cells (DCs) in the lymph nodes migrate and infiltrate into the target tissues where their reactivation by peripheral tissue antigen is a prerequisite for effector cytokine production and tissue destruction. The target tissue microenvironment, as well as the local microenvironment at the immune synapse formed by T cells that encounter cognate antigen presenting cells (APCs) shave recently emerged as critical factors in shaping the differentiation and function of self-reactive effector T cells, providing the signals required for their activation in the form of the self-antigen and cytokine milieu...
February 2, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28152566/exacerbation-of-spontaneous-autoimmune-nephritis-following-regulatory-t-cell-depletion-in-bim-knockout-mice
#6
Yuan Min Wang, Geoff Yu Zhang, Ya Wang, Min Hu, Jimmy Jianheng Zhou, Andrew Sawyer, Qi Cao, Yiping Wang, Guoping Zheng, Vincent W S Lee, David C H Harris, Stephen I Alexander
Regulatory T cells (Tregs) have been recognised as central mediators for maintaining peripheral tolerance and limiting autoimmune diseases. Loss of Tregs or their function has been associated with exacerbation of autoimmune disease. However, the temporary loss of Tregs in chronic spontaneous disease model has not been investigated. In this study, we evaluated the role of Tregs in a novel chronic spontaneous glomerulonephritis model of B cell lymphoma 2-interacting mediator (Bim) knockout mice by transient depleting Tregs...
February 2, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28131824/a-dynamic-model-of-immune-responses-to-antigen-presentation-predicts-different-regions-of-tumor-or-pathogen-elimination
#7
Eduardo D Sontag
The immune system must discriminate between agents of disease and an organism's healthy cells. While the identification of an antigen as self/non-self is critically important, the dynamic features of antigen presentation may also determine the immune system's response. Here, we use a simple mathematical model of immune activation to explore the idea of antigen discrimination through dynamics. We propose that antigen presentation is coupled to two nodes, one regulatory and one effecting the immune response, through an incoherent feedforward loop and repressive feedback...
January 25, 2017: Cell Systems
https://www.readbyqxmd.com/read/28128086/vesicular-contact-reaction-may-progress-into-erythema-multiforme
#8
Magdalena Czarnecka-Operacz, Dorota Jenerowicz, Joanna Szulczyńska-Gabor, Ewa Teresiak-Mikołajczak, Joanna Szyfter-Harris, Monika Bowszyc-Dmochowska
Dear Editor, Erythema multiforme is considered an acute skin condition, characterized by a self-limiting and sometimes recurrent course. It is regarded as a type IV hypersensitivity reaction associated with certain infections, medications, and other various triggers. Allergic contact dermatitis is in turn a delayed type of induced allergy as a result of cutaneous contact with a specific allergen to which the patient develops specific sensitivity. This type of cutaneous reaction is associated with inflammation manifesting with erythema, edema, and vesicles...
December 2016: Acta Dermatovenerologica Croatica: ADC
https://www.readbyqxmd.com/read/28115591/type-ii-nkt-cells-and-their-emerging-role-in-health-and-disease
#9
REVIEW
Madhav V Dhodapkar, Vipin Kumar
NKT cells recognize lipid Ags presented by a class I MHC-like molecule CD1d, a member of the CD1 family. Although most initial studies on NKT cells focused on a subset with semi-invariant TCR termed invariant NKT cells, the majority of CD1d-restricted lipid-reactive human T cells express diverse TCRs and are termed type II NKT cells. These cells constitute a distinct population of circulating and tissue-resident effector T cells with immune-regulatory properties. They react to a growing list of self- as well as non-self-lipid ligands, and share some properties with both invariant NKT and conventional T cells...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28108558/irf4-expression-in-thymic-epithelium-is-critical-for-thymic-regulatory-t-cell-homeostasis
#10
Uku Haljasorg, James Dooley, Martti Laan, Kai Kisand, Rudolf Bichele, Adrian Liston, Pärt Peterson
The thymus is a primary lymphoid organ required for the induction and maintenance of central tolerance. The main function of the thymus is to generate an immunocompetent set of T cells not reactive to self. During negative selection in the thymus, thymocytes with autoreactive potential are either deleted or differentiated into regulatory T cells (Tregs). The molecular basis by which the thymus allows high-efficiency Treg induction remains largely unknown. In this study, we report that IFN regulatory factor 4 (Irf4) is highly expressed in murine thymic epithelium and is required to prime thymic epithelial cells (TEC) for effective Treg induction...
January 20, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28108025/viral-induced-suppression-of-self-reactive-t-cells-lessons-from-neurotropic-coronavirus-induced-demyelination
#11
REVIEW
Carine Savarin, Cornelia C Bergmann
Genetic and environmental factors, i.e. infections, have been proposed to contribute to disease induction and relapsing events in multiple sclerosis (MS), an autoimmune demyelinating disease of the central nervous system (CNS). While research has mainly focused on virus associated autoimmune activation, less is known about prevention of autoimmunity, especially following resolving infections associated with CNS tissue damage. This review discusses novel insights on control of self-reactive (SR) T cells activated during neurotropic coronavirus-induced demyelination...
January 11, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28081217/collective-genetic-interaction-effects-and-the-role-of-antigen-presenting-cells-in-autoimmune-diseases
#12
Hyung Jun Woo, Chenggang Yu, Jaques Reifman
Autoimmune diseases occur when immune cells fail to develop or lose their tolerance toward self and destroy body's own tissues. Both insufficient negative selection of self-reactive T cells and impaired development of regulatory T cells preventing effector cell activation are believed to contribute to autoimmunity. Genetic predispositions center around the major histocompatibility complex (MHC) class II loci involved in antigen presentation, the key determinant of CD4+ T cell activation. Recent studies suggested that variants in the MHC region also exhibit significant non-additive interaction effects...
2017: PloS One
https://www.readbyqxmd.com/read/28066981/disruption-of-transplant-tolerance-by-an-incognito-form-of-cd8-t-cell-dependent-memory
#13
M K Nelsen, K S Beard, R J Plenter, R M Kedl, E T Clambey, R G Gill
Several approaches successfully achieve allograft tolerance in preclinical models but are challenging to translate into clinical practice. Many clinically relevant factors can attenuate allograft tolerance induction including intrinsic genetic resistance, peri-transplant infection, inflammation, and pre-existing anti-donor immunity. The prevailing view for immune memory as a tolerance barrier is that the host harbors memory cells that spontaneously cross-react to donor MHC antigens. Such pre-existing 'heterologous' memory cells have direct reactivity to donor cells and resist most tolerance regimens...
January 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28044415/modulation-of-alloimmune-response-by-commensal-gut-microbiota-and-potential-new-avenues-to-influence-the-outcome-of-allogeneic-transplantation-by-modification-of-the-gut-culture
#14
REVIEW
S Kanangat
Host defence response against microbial infections was the foundation for the Science of Immunology. Now, we know the mechanisms of such host defence which include innate immune responses that is generally nonspecific but effective in many cases and lead to more specific responses called adaptive immune response. The gene loci of class I, II and III of the major histocompatibility complex (MHC) play a major role in directing the adaptive immune responses by presenting processed antigens to T and B cells to induce appropriate antigen-specific cellular and or humoral immune responses...
January 3, 2017: International Journal of Immunogenetics
https://www.readbyqxmd.com/read/28018338/the-pd1-pd-l1-2-pathway-from-discovery-to-clinical-implementation
#15
REVIEW
Kankana Bardhan, Theodora Anagnostou, Vassiliki A Boussiotis
The immune system maintains a critically organized network to defend against foreign particles, while evading self-reactivity simultaneously. T lymphocytes function as effectors and play an important regulatory role to orchestrate the immune signals. Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. The immune system evolved various mechanisms to constrain such autoreactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (TRegs)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28013554/the-emerging-roles-of-b-cells-as-partners-and-targets-in-periodontitis
#16
Moncef Zouali
Initial studies of periodontal disease suggested that T cell-mediated immunity against oral Gram-negative microorganisms is a key player in the pathogenesis of this inflammatory disease. Recent investigations, however, revealed that B cells are also engaged. Given their chief role in innate-like and adaptive immune responses, B cells could exert protective functions in periodontitis. However, the periodontal bacteria-specific antibody response is generally unable to halt disease progression in affected subjects, suggesting that the antibodies produced could exhibit low anti-bacterial blocking functions or opsonophagocytic potential, and/or unfavorable effects...
December 26, 2016: Autoimmunity
https://www.readbyqxmd.com/read/27920090/islet-derived-cd4-t-cells-targeting-proinsulin-in-human-autoimmune-diabetes
#17
Aaron W Michels, Laurie G Landry, Kristen A McDaniel, Liping Yu, Martha Campbell-Thompson, William W Kwok, Kenneth L Jones, Peter A Gottlieb, John W Kappler, Qizhi Tang, Bart O Roep, Mark A Atkinson, Clayton E Mathews, Maki Nakayama
Type 1 diabetes results from chronic autoimmune destruction of insulin-producing beta cells within pancreatic islets. While insulin is a critical self-antigen in animal models of autoimmune diabetes, due to extremely limited access to pancreas samples, little is known about human antigenic targets for islet-infiltrating T-cells. Here we show that proinsulin peptides are targeted by islet-infiltrating T-cells from type 1 diabetes patients. We identified hundreds of T-cells from inflamed pancreatic islets of three young type 1 diabetes organ donors with a short disease duration with high risk HLA genes using a direct T-cell receptor (TCR) sequencing approach without long-term cell culture...
December 5, 2016: Diabetes
https://www.readbyqxmd.com/read/27917626/association-of-new-putative-epitopes-of-myelin-proteolipid-protein-58-74-with-pathogenesis-of-multiple-sclerosis
#18
Zahra Zamanzadeh, Ghasem Ahangari, Mitra Ataei, Samie Pouragahi, Seyed Massood Nabavi, Mehdi Sadeghi, Mohammad Hossein Sanati
Multiple sclerosis (MS) is an autoimmune disease in which auto-reactive T cells react with self-antigens expressed in the central nervous system (CNS). The main cause of MS is unknown. Nonetheless, the most probable theory is based on molecular mimicry, which suggests that some infections can activate T cells against brain auto-antigens like myelin proteolipid protein (PLP) and initiate the disease cascade. This study is conducted to evaluate the activatory effects of PLP58-74 on T lymphocytes and humoral immunity...
October 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27904889/reactive-oxygen-species-in-bcr-abl1-expressing-cells-relevance-to-chronic-myeloid-leukemia
#19
Joanna Antoszewska-Smith, Elzbieta Pawlowska, Janusz Blasiak
Chronic myeloid leukemia (CML) results from the t(9;22) reciprocal chromosomal translocation producing the BCR-ABL1 gene, conferring growth and proliferation advantages in the CML cells. CML progresses from chronic, often syndrome-free, to blast phase, fatal if not treated. Although the involvement of BCR-ABL1 in some signaling pathways is considered as the cause of CML, the mechanisms resulting in its progression are not completely known. However, BCR-ABL1 stimulates the production of reactive oxygen species (ROS), which levels increase with CML progression and induce BCR-ABL1 self-mutagenesis...
December 1, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27903651/t-cells-encountering-myeloid-cells-programmed-for-amino-acid-dependent-immunosuppression-use-rictor-mtorc2-protein-for-proliferative-checkpoint-decisions
#20
Lee-Ann Van de Velde, Chitra Subramanian, Amber M Smith, Luke Barron, Joseph E Qualls, Geoffrey Neale, Adolfo Alfonso-Pecchio, Suzanne Jackowski, Charles O Rock, Thomas A Wynn, Peter J Murray
Modulation of T cell proliferation and function by immunoregulatory myeloid cells are an essential means of preventing self-reactivity and restoring tissue homeostasis. Consumption of amino acids such as arginine and tryptophan by immunoregulatory macrophages is one pathway that suppresses local T cell proliferation. Using a reduced complexity in vitro macrophage-T cell co-culture system, we show that macrophage arginase-1 is the only factor required by M2 macrophages to block T cells in G1, and this effect is mediated by l-arginine elimination rather than metabolite generation...
January 6, 2017: Journal of Biological Chemistry
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