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https://www.readbyqxmd.com/read/29401462/synthesis-stabilization-and-characterization-of-the-mr1-ligand-precursor-5-amino-6-d-ribitylaminouracil-5-a-ru
#1
Kelin Li, Charles K Vorkas, Ashutosh Chaudhry, Donielle L Bell, Richard A Willis, Alexander Rudensky, John D Altman, Michael S Glickman, Jeffrey Aubé
Mucosal-associated invariant T (MAIT) cells are an abundant class of innate T cells restricted by the MHC I-related molecule MR1. MAIT cells can recognize bacterially-derived metabolic intermediates from the riboflavin pathway presented by MR1 and are postulated to play a role in innate antibacterial immunity through production of cytokines and direct bacterial killing. MR1 tetramers, typically stabilized by the adduct of 5-amino-6-D-ribitylaminouracil (5-A-RU) and methylglyoxal (MeG), are important tools for the study of MAIT cells...
2018: PloS One
https://www.readbyqxmd.com/read/29339377/robust-antitumor-responses-result-from-local-chemotherapy-and-ctla-4-blockade
#2
Charlotte E Ariyan, Mary Sue Brady, Robert H Siegelbaum, Jian Hu, Danielle M Bello, Jamie Green, Charles Fisher, Robert A Lefkowitz, Katherine S Panageas, Melissa Pulitzer, Marissa Vignali, Ryan Emerson, Christopher Tipton, Harlan Robins, Taha Merghoub, Jianda Yuan, Achim Jungbluth, Jorge Blando, Padmanee Sharma, Alexander Y Rudensky, Jedd D Wolchok, James P Allison
Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a non-inflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29080364/comparative-analysis-of-murine-t-cell-receptor-repertoires
#3
REVIEW
Mark Izraelson, Tatiana O Nakonechnaya, Bruno Moltedo, Evgeniy S Egorov, Sofya A Kasatskaya, Ekaterina V Putintseva, Ilgar Z Mamedov, Dmitriy B Staroverov, Irina I Shemiakina, Maria Y Zakharova, Alexey N Davydov, Dmitriy A Bolotin, Mikhail Shugay, Dmitriy M Chudakov, Alexander Y Rudensky, Olga V Britanova
On the way of understanding the rules and laws of adaptive immunity, high-throughput profiling of TCR repertoires becomes a powerful tool. The structure of TCR repertoires is insightful and instructive even before antigen specificity of each particular receptor becomes available. It embodies information about the thymic and peripheral selection of T cells, about the readiness of an adaptive immunity to withstand new challenges, about the character, the magnitude, and the memory of immune response, and about the etiological and functional proximity of T cell subsets...
October 28, 2017: Immunology
https://www.readbyqxmd.com/read/29038367/a-nonimmune-function-of-t-cells-in-promoting-lung-tumor-progression
#4
Jesse A Green, Nicholas Arpaia, Michail Schizas, Anton Dobrin, Alexander Y Rudensky
The involvement of effector T cells and regulatory T (T reg) cells in opposing and promoting solid organ carcinogenesis, respectively, is viewed as a shifting balance between a breach versus establishment of tolerance to tumor or self-antigens. We considered that tumor-associated T cells might promote malignancy via distinct mechanisms used by T cells in nonlymphoid organs to assist in their maintenance upon injury or stress. Recent studies suggest that T reg cells can participate in tissue repair in a manner separable from their immunosuppressive capacity...
October 16, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29037524/t-regulatory-cells-triumph-of-perseverance-the-crafoord-prize-for-polyarthritis-in-2017
#5
REVIEW
Frank A Wollheim
The Crafoord Prize in Polyarthritis ranks as one of the most prestigious prizes and can be awarded only if the Royal Swedish Academy of Sciences decides the likelihood of prize worthy progress in the field, and at most every 4th year. This has happened only four times since 1982. This year the 5th Laureates were Shimon Sakaguchi, Fred Ramsdell, and Alexander Rudensky with the motivation "for their discoveries relating to regulatory T cells, which counteract harmful immune reactions in arthritis and other autoimmune diseases"...
September 6, 2017: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/29020005/antigen-receptor-repertoire-profiling-from-rna-seq-data
#6
Dmitriy A Bolotin, Stanislav Poslavsky, Alexey N Davydov, Felix E Frenkel, Lorenzo Fanchi, Olga I Zolotareva, Saskia Hemmers, Ekaterina V Putintseva, Anna S Obraztsova, Mikhail Shugay, Ravshan I Ataullakhanov, Alexander Y Rudensky, Ton N Schumacher, Dmitriy M Chudakov
No abstract text is available yet for this article.
October 11, 2017: Nature Biotechnology
https://www.readbyqxmd.com/read/28953866/corrigendum-stability-and-function-of-regulatory-t-cells-expressing-the-transcription-factor-t-bet
#7
Andrew G Levine, Alejandra Mendoza, Saskia Hemmers, Bruno Moltedo, Rachel E Niec, Michail Schizas, Beatrice E Hoyos, Ekaterina V Putintseva, Ashutosh Chaudhry, Stanislav Dikiy, Sho Fujisawa, Dmitriy M Chudakov, Piper M Treuting, Alexander Y Rudensky
This corrects the article DOI: 10.1038/nature22360.
September 20, 2017: Nature
https://www.readbyqxmd.com/read/28724724/brct-domain-protein-brit1-influences-class-switch-recombination
#8
Wei-Feng Yen, Ashutosh Chaudhry, Bharat Vaidyanathan, William T Yewdell, Joseph N Pucella, Rahul Sharma, Yulong Liang, Kaiyi Li, Alexander Y Rudensky, Jayanta Chaudhuri
DNA double-strand breaks (DSBs) serve as obligatory intermediates for Ig heavy chain (Igh) class switch recombination (CSR). The mechanisms by which DSBs are resolved to promote long-range DNA end-joining while suppressing genomic instability inherently associated with DSBs are yet to be fully elucidated. Here, we use a targeted short-hairpin RNA screen in a B-cell lymphoma line to identify the BRCT-domain protein BRIT1 as an effector of CSR. We show that conditional genetic deletion of BRIT1 in mice leads to a marked increase in unrepaired Igh breaks and a significant reduction in CSR in ex vivo activated splenic B cells...
July 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28607488/stability-and-function-of-regulatory-t-cells-expressing-the-transcription-factor-t-bet
#9
Andrew G Levine, Alejandra Medoza, Saskia Hemmers, Bruno Moltedo, Rachel E Niec, Michail Schizas, Beatrice E Hoyos, Ekaterina V Putintseva, Ashutosh Chaudhry, Stanislav Dikiy, Sho Fujisawa, Dmitriy M Chudakov, Piper M Treuting, Alexander Y Rudensky
Adaptive immune responses are tailored to different types of pathogens through differentiation of naive CD4 T cells into functionally distinct subsets of effector T cells (T helper 1 (TH1), TH2, and TH17) defined by expression of the key transcription factors T-bet, GATA3, and RORγt, respectively. Regulatory T (Treg) cells comprise a distinct anti-inflammatory lineage specified by the X-linked transcription factor Foxp3 (refs 2, 3). Paradoxically, some activated Treg cells express the aforementioned effector CD4 T cell transcription factors, which have been suggested to provide Treg cells with enhanced suppressive capacity...
June 15, 2017: Nature
https://www.readbyqxmd.com/read/28130403/suppression-of-lethal-autoimmunity-by-regulatory-t-cells-with-a-single-tcr-specificity
#10
Andrew G Levine, Saskia Hemmers, Antonio P Baptista, Michail Schizas, Mehlika B Faire, Bruno Moltedo, Catherine Konopacki, Marc Schmidt-Supprian, Ronald N Germain, Piper M Treuting, Alexander Y Rudensky
The regulatory T cell (T reg cell) T cell receptor (TCR) repertoire is highly diverse and skewed toward recognition of self-antigens. TCR expression by T reg cells is continuously required for maintenance of immune tolerance and for a major part of their characteristic gene expression signature; however, it remains unknown to what degree diverse TCR-mediated interactions with cognate self-antigens are required for these processes. In this study, by experimentally switching the T reg cell TCR repertoire to a single T reg cell TCR, we demonstrate that T reg cell function and gene expression can be partially uncoupled from TCR diversity...
March 6, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28115587/pillars-article-foxp3-programs-the-development-and-function-of-cd4-cd25-regulatory-t-cells-nat-immunol-2003-4-330-336
#11
Jason D Fontenot, Marc A Gavin, Alexander Y Rudensky
No abstract text is available yet for this article.
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28011866/the-aryl-hydrocarbon-receptor-controls-cell-fate-decisions-in-b-cells
#12
Bharat Vaidyanathan, Ashutosh Chaudhry, William T Yewdell, Davide Angeletti, Wei-Feng Yen, Adam K Wheatley, Christopher A Bradfield, Adrian B McDermott, Jonathan W Yewdell, Alexander Y Rudensky, Jayanta Chaudhuri
Generation of cellular heterogeneity is an essential feature of the adaptive immune system. This is best exemplified during humoral immune response when an expanding B cell clone assumes multiple cell fates, including class-switched B cells, antibody-secreting plasma cells, and memory B cells. Although each cell type is essential for immunity, their generation must be exquisitely controlled because a class-switched B cell cannot revert back to the parent isotype, and a terminally differentiated plasma cell cannot contribute to the memory pool...
January 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27879269/basophils-promote-tumor-rejection-via-chemotaxis-and-infiltration-of-cd8-t-cells
#13
Ibrahim M Sektioglu, Rafael Carretero, Nadja Bulbuc, Tobias Bald, Thomas Tüting, Alexander Y Rudensky, Günter J Hämmerling
Elevated numbers of regulatory T cells (Treg) in patient tumors are known to inhibit efficient antitumor T-cell responses. To study the mechanisms controlling tumor rejection, we assessed different mouse models for Treg depletion. In Foxp3DTR knock-in mice, about 99% Treg depletion was achieved, resulting in complete rejection of transplanted HCmel12 melanomas in a CD8(+) T-cell-dependent way. In contrast, about 90% Treg depletion obtained in BAC transgenic Foxp3.LuciDTR4 mice failed to induce complete rejection of HCmel12 melanomas, demonstrating that residual Tregs were able to control CD8(+) T-cell responses against the tumor...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/27851913/regulatory-t-cells-exhibit-distinct-features-in-human-breast-cancer
#14
George Plitas, Catherine Konopacki, Kenmin Wu, Paula D Bos, Monica Morrow, Ekaterina V Putintseva, Dmitriy M Chudakov, Alexander Y Rudensky
Regulatory T (Treg) cells reside in lymphoid organs and barrier tissues where they control different types of inflammatory responses. Treg cells are also found in human cancers, and studies in animal models suggest that they contribute to cancer progression. However, properties of human intratumoral Treg cells and those present in corresponding normal tissue remain largely unknown. Here, we analyzed features of Treg cells in untreated human breast carcinomas, normal mammary gland, and peripheral blood. Tumor-resident Treg cells were potently suppressive and their gene-expression pattern resembled that of normal breast tissue, but not of activated peripheral blood Treg cells...
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27595233/an-essential-role-for-the-il-2-receptor-in-treg-cell-function
#15
Takatoshi Chinen, Arun K Kannan, Andrew G Levine, Xiying Fan, Ulf Klein, Ye Zheng, Georg Gasteiger, Yongqiang Feng, Jason D Fontenot, Alexander Y Rudensky
Regulatory T cells (Treg cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by Treg cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the Treg cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of Treg cells...
November 2016: Nature Immunology
https://www.readbyqxmd.com/read/27590281/regulatory-t-cells-differentiation-and-function
#16
REVIEW
George Plitas, Alexander Y Rudensky
The immune system of vertebrate animals has evolved to mount an effective defense against a diverse set of pathogens while minimizing transient or lasting impairment in tissue function that could result from the inflammation caused by immune responses to infectious agents. In addition, misguided immune responses to "self" and dietary antigens, as well as to commensal microorganisms, can lead to a variety of inflammatory disorders, including autoimmunity, metabolic syndrome, allergies, and cancer. Regulatory T cells expressing the X chromosome-linked transcription factor Foxp3 suppress inflammatory responses in diverse biological settings and serve as a vital mechanism of negative regulation of immune-mediated inflammation...
September 2, 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27584728/a-conversation-with-alexander-rudensky
#17
Ushma S Neill
No abstract text is available yet for this article.
September 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27499023/memory-of-inflammation-in-regulatory-t-cells
#18
Joris van der Veeken, Alvaro J Gonzalez, Hyunwoo Cho, Aaron Arvey, Saskia Hemmers, Christina S Leslie, Alexander Y Rudensky
Eukaryotic cells can "remember" transient encounters with a wide range of stimuli, inducing lasting states of altered responsiveness. Regulatory T (Treg) cells are a specialized lineage of suppressive CD4 T cells that act as critical negative regulators of inflammation in various biological contexts. Treg cells exposed to inflammatory conditions acquire strongly enhanced suppressive function. Using inducible genetic tracing, we analyzed the long-term stability of activation-induced transcriptional, epigenomic, and functional changes in Treg cells...
August 11, 2016: Cell
https://www.readbyqxmd.com/read/27026074/t-cell-receptor-signalling-in-the-control-of-regulatory-t-cell-differentiation-and-function
#19
REVIEW
Ming O Li, Alexander Y Rudensky
Regulatory T cells (TReg cells), a specialized T cell lineage, have a pivotal function in the control of self tolerance and inflammatory responses. Recent studies have revealed a discrete mode of T cell receptor (TCR) signalling that regulates TReg cell differentiation, maintenance and function and that affects gene expression, metabolism, cell adhesion and migration of these cells. Here, we discuss the emerging understanding of TCR-guided differentiation of TReg cells in the context of their function in health and disease...
April 2016: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/26967286/hallmarks-of-tissue-resident-lymphocytes
#20
REVIEW
Xiying Fan, Alexander Y Rudensky
Although they are classically viewed as continuously recirculating through the lymphoid organs and blood, lymphocytes also establish residency in non-lymphoid tissues, most prominently at barrier sites, including the mucosal surfaces and skin. These specialized tissue-resident lymphocyte subsets span the innate-adaptive continuum and include innate lymphoid cells (ILCs), unconventional T cells (e.g., NKT, MAIT, γδ T cells, and CD8αα(+) IELs), and tissue-resident memory T (T(RM)) cells. Although these diverse cell types differ in the particulars of their biology, they nonetheless exhibit important shared features, including a role in the preservation of tissue integrity and function during homeostasis, infection, and non-infectious perturbations...
March 10, 2016: Cell
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