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Understanding immunology

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12 papers 25 to 100 followers
https://www.readbyqxmd.com/read/26319196/effector-t-cell-differentiation-are-master-regulators-of-effector-t-cells-still-the-masters
#1
REVIEW
Chao Wang, Mary Collins, Vijay K Kuchroo
Effector CD4 T cell lineages have been implicated as potent inducers of autoimmune diseases. Tbet, Gata3 and Rorgt are master transcriptional regulators of Th1, Th2 and Th17 lineages respectively and promote the distinct expression of signature cytokines. Significant progress has been made in understanding the transcriptional network that drives CD4 T cell differentiation, revealing novel points of regulation mediated by transcription factors, cell surface receptors, cytokines and chemokines. Epigenetic modifications and metabolic mediators define the transcriptional landscape in which master transcription factors operate and collaborate with a network of transcriptional modifiers to guide lineage specification, plasticity and function...
December 2015: Current Opinion in Immunology
https://www.readbyqxmd.com/read/26426795/il-2-and-il-15-regulate-cd8-memory-t-cell-differentiation-but-are-dispensable-for-protective-recall-responses
#2
Cédric Mathieu, Jean-Christophe Beltra, Tania Charpentier, Sara Bourbonnais, James P Di Santo, Alain Lamarre, Hélène Decaluwe
The ability to mount effective secondary responses is a cardinal feature of memory CD8(+) T cells. An understanding of the factors that regulate the generation and recall capacities of memory T cells remains to be ascertained. Several cues indicate that two highly related cytokines, IL-2 and IL-15, share redundant functions in this process. To establish their combined roles in memory CD8(+) T-cell development, maintenance, and secondary responses, we compared the outcome of adoptively transferred IL2Rβ(+/-) or IL2Rβ(-/-) CD8(+) T cells after an acute viral infection in mice...
December 2015: European Journal of Immunology
https://www.readbyqxmd.com/read/26431533/the-timing-of-stimulation-and-il-2-signaling-regulate-secondary-cd8-t-cell-responses
#3
Shaniya H Khan, Matthew D Martin, Gabriel R Starbeck-Miller, Hai-Hui Xue, John T Harty, Vladimir P Badovinac
Memory CD8 T cells provide protection to immune hosts by eliminating pathogen-infected cells during re-infection. While parameters influencing the generation of primary (1°) CD8 T cells are well established, the factors controlling the development of secondary (2°) CD8 T cell responses remain largely unknown. Here, we address the mechanisms involved in the generation and development of 2° memory (M) CD8 T cells. We observed that the time at which 1° M CD8 T cells enter into immune response impacts their fate and differentiation into 2° M CD8 T cells...
October 2015: PLoS Pathogens
https://www.readbyqxmd.com/read/24958858/androgens-alter-t-cell-immunity-by-inhibiting-t-helper-1-differentiation
#4
Haydn T Kissick, Martin G Sanda, Laura K Dunn, Kathryn L Pellegrini, Seung T On, Jonathan K Noel, Mohamed S Arredouani
The hormonal milieu influences immune tolerance and the immune response against viruses and cancer, but the direct effect of androgens on cellular immunity remains largely uncharacterized. We therefore sought to evaluate the effect of androgens on murine and human T cells in vivo and in vitro. We found that murine androgen deprivation in vivo elicited RNA expression patterns conducive to IFN signaling and T-cell differentiation. Interrogation of mechanism showed that testosterone regulates T-helper 1 (Th1) differentiation by inhibiting IL-12-induced Stat4 phosphorylation: in murine models, we determined that androgen receptor binds a conserved region within the phosphatase, Ptpn1, and consequent up-regulation of Ptpn1 then inhibits IL-12 signaling in CD4 T cells...
July 8, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25674089/five-layers-of-receptor-signaling-in-%C3%AE-%C3%AE-t-cell-differentiation-and-activation
#5
REVIEW
Sérgio T Ribeiro, Julie C Ribot, Bruno Silva-Santos
The contributions of γδ T-cells to immunity to infection or tumors critically depend on their activation and differentiation into effectors capable of secreting cytokines and killing infected or transformed cells. These processes are molecularly controlled by surface receptors that capture key extracellular cues and convey downstream intracellular signals that regulate γδ T-cell physiology. The understanding of how environmental signals are integrated by γδ T-cells is critical for their manipulation in clinical settings...
2015: Frontiers in Immunology
https://www.readbyqxmd.com/read/20434894/effector-and-memory-cd8-t-cell-differentiation-toward-a-molecular-understanding-of-fate-determination
#6
REVIEW
Gabrielle T Belz, Axel Kallies
CD8(+) T cells play a key role in protecting the body against invading microorganisms. Their capacity to control infection relies on the development of peripheral effector and memory T cells. Much of our current knowledge has been gained by tracking alterations of the phenotype of CD8(+) T cells but the molecular understanding of the events that underpin the emergence of heterogeneous effector and memory CD8(+) T cells in response to infection has remained limited. This review focuses on the recent progress in our understanding of the molecular wiring of this differentiation process...
June 2010: Current Opinion in Immunology
https://www.readbyqxmd.com/read/27064374/asymmetric-inheritance-of-mtorc1-kinase-activity-during-division-dictates-cd8-t-cell-differentiation
#7
Kristen N Pollizzi, Im-Hong Sun, Chirag H Patel, Ying-Chun Lo, Min-Hee Oh, Adam T Waickman, Ada J Tam, Richard L Blosser, Jiayu Wen, Greg M Delgoffe, Jonathan D Powell
The asymmetric partitioning of fate-determining proteins has been shown to contribute to the generation of CD8(+) effector and memory T cell precursors. Here we demonstrate the asymmetric partitioning of mTORC1 activity after the activation of naive CD8(+) T cells. This results in the generation of two daughter T cells, one of which shows increased mTORC1 activity, increased glycolytic activity and increased expression of effector molecules. The other daughter T cell has relatively low mTORC1 activity and increased lipid metabolism, expresses increased amounts of anti-apoptotic molecules and subsequently displays enhanced long-term survival...
June 2016: Nature Immunology
https://www.readbyqxmd.com/read/25257362/t-cell-differentiation-in-chronic-infection-and-cancer-functional-adaptation-or-exhaustion
#8
REVIEW
Daniel E Speiser, Daniel T Utzschneider, Susanne G Oberle, Christian Münz, Pedro Romero, Dietmar Zehn
Chronic viral infections and malignant tumours induce T cells that have a reduced ability to secrete effector cytokines and have upregulated expression of the inhibitory receptor PD1 (programmed cell death protein 1). These features have so far been considered to mark terminally differentiated 'exhausted' T cells. However, several recent clinical and experimental observations indicate that phenotypically exhausted T cells can still mediate a crucial level of pathogen or tumour control. In this Opinion article, we propose that the exhausted phenotype results from a differentiation process in which T cells stably adjust their effector capacity to the needs of chronic infection...
November 2014: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/25396352/molecular-regulation-of-effector-and-memory-t-cell-differentiation
#9
REVIEW
John T Chang, E John Wherry, Ananda W Goldrath
Immunological memory is a cardinal feature of adaptive immunity and an important goal of vaccination strategies. Here we highlight advances in the understanding of the diverse T lymphocyte subsets that provide acute and long-term protection from infection. These include new insights into the transcription factors, and the upstream 'pioneering' factors that regulate their accessibility to key sites of gene regulation, as well as metabolic regulators that contribute to the differentiation of effector and memory subsets; ontogeny and defining characteristics of tissue-resident memory lymphocytes; and origins of the remarkable heterogeneity exhibited by activated T cells...
December 2014: Nature Immunology
https://www.readbyqxmd.com/read/28627520/unique-aspects-of-the-perinatal-immune-system
#10
REVIEW
Xiaoming Zhang, Dania Zhivaki, Richard Lo-Man
The early stages of life are associated with increased susceptibility to infection, which is in part due to an ineffective immune system. In the context of infection, the immune system must be stimulated to provide efficient protection while avoiding insufficient or excessive activation. Yet, in early life, age-dependent immune regulation at molecular and cellular levels contributes to a reduced immunological fitness in terms of pathogen clearance and response to vaccines. To enable microbial colonization to be tolerated at birth, epigenetic immune cell programming and early life-specific immune regulatory and effector mechanisms ensure that vital functions and organ development are supported and that tissue damage is avoided...
August 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/27548616/redirecting-specificity-of-t-cells-using-the-sleeping-beauty-system-to-express-chimeric-antigen-receptors-by-mix-and-matching-of-vl-and-vh-domains-targeting-cd123-tumors
#11
Radhika Thokala, Simon Olivares, Tiejuan Mi, Sourindra Maiti, Drew Deniger, Helen Huls, Hiroki Torikai, Harjeet Singh, Richard E Champlin, Tamara Laskowski, George McNamara, Laurence J N Cooper
Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains...
2016: PloS One
https://www.readbyqxmd.com/read/22206779/advances-in-basic-and-clinical-immunology-in-2011
#12
REVIEW
Javier Chinen, William T Shearer
Investigations of basic immunologic mechanisms and clinical studies of primary immunodeficiencies were most prevalent in 2011. Significant progress was achieved in the characterization of T(H)17 cell differentiation and associated cytokines in the setting of inflammatory disorders, HIV infection, and immunodysregulation disorders. The role of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) mutations in the pathogenesis of CVID was further described and reported to be likely mediated by impaired TACI expression affecting B-cell function...
February 2012: Journal of Allergy and Clinical Immunology
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