DOCSLIB.ORG

Chronic Viral Infection in Mice Ligand Expression on APC Subsets Over

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chronic Viral Infection in Mice Ligand Expression on APC Subsets Over Conserved and Differential Features of TNF Superfamily Ligand Expression on APC Subsets over the Course of a Chronic Viral Infection in Mice Kuan C. Wang, Kuan-Lun Chu, Nathalia V. Batista and Tania H. Watts Downloaded from ImmunoHorizons 2018, 2 (11) 407-417 doi: https://doi.org/10.4049/immunohorizons.1800047 http://www.immunohorizons.org/content/2/11/407 http://www.immunohorizons.org/ This information is current as of October 3, 2021. Supplementary http://www.immunohorizons.org/content/suppl/2018/12/20/2.11.407.DCSup Material plemental References This article cites 33 articles, 10 of which you can access for free at: http://www.immunohorizons.org/content/2/11/407.full#ref-list-1 Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: by guest on October 3, 2021 http://www.immunohorizons.org/alerts ImmunoHorizons is an open access journal published by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. ISSN 2573-7732. RESEARCH ARTICLE Infectious Disease Conserved and Differential Features of TNF Superfamily Ligand Expression on APC Subsets over the Course of a Chronic Viral Infection in Mice Kuan C. Wang, Kuan-Lun Chu, Nathalia V. Batista, and Tania H. Watts Downloaded from Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada ABSTRACT http://www.immunohorizons.org/ There is currently much interest in how different APC subsets shape the immune response. We recently described a division of labor between classical dendritic cells (cDC) and inflammatory monocyte-derived APC in provision of costimulatory ligands to T cells early during chronic lymphocytic choriomeningitis clone 13 (LCMV 13) infection in mice. At day 2 of LCMV 13 infection, cDC preferentially express CD80 and CD86, whereas TNF superfamily ligands GITRL, 4-1BBL, CD70, and OX40L are preferentially induced by type I IFN on inflammatory monocyte-derived APC, with minimal expression on cDC. In this study, we further investigate the expression of TNF and B7 family ligands on APC over the course of LCMV 13 infection. OX40L and 4-1BBL remain above baseline through the chronic stage of infection, with predominant expression on inflammatory APC compared with cDC in the spleen, partially blocked by anti–IFN-gR Ab pretreatment. Conversely, CD70, like GITRL, returns to baseline on the APC within a few days postinfection. In the lung, TNF family ligands were also preferentially expressed on inflammatory monocyte-derived APC. CD86 was generally higher on cDC than inflammatory APC in the spleen, but in the lung CD86 was highest on inflammatory APC. Moreover, in the spleen, CD80 by guest on October 3, 2021 levels on different APC subsets fluctuated over the course of the infection. We also show that LPS induction of TNF superfamily ligands is largely mediated through type I IFN. This study highlights the importance of IFNs and monocyte-derived APC in TNF superfamily ligand expression in both secondary lymphoid organs and tissues during chronic viral infection. ImmunoHorizons, 2018, 2: 407–417. INTRODUCTION of the TNF superfamily contribute to T cell activation by providing survival signals to sustain T cell accumulation (4, 5). Recently, our T cell priming requires the recognition of peptide–MHC by the laboratory provided evidence that there is a division of labor Ag-specific TCR (signal 1) as well as corecognition of B7 family between different APC subsets in providing costimulatory costimulatory ligands (CD80, CD86) binding to CD28 (signal 2) (1). molecules to T cells (6). We showed that at day 2 of lymphocytic Cytokines produced early during infection also play a pivotal role choriomeningitis (LCMV) clone 13 infection in the spleen or day 3 in induction of the costimulatory ligands as well as in providing of influenza A infection in the draining lymph node, cell-specific signals for T cell differentiation and expansion (signal 3) (2, 3). In effects of type I IFN (IFN-I) resulted in a dichotomy of expression addition to the B7 family of costimulatory ligands, several members of TNF versus B7 superfamily ligands on different APC subsets. Received for publication July 11, 2018. Accepted for publication November 29, 2018. Address correspondence and reprint request to: Dr. Tania H. Watts, University of Toronto, Department of Immunology, Medical Sciences Building, Room 7221, 1 King’s College Circle, Toronto, ON M5S 1A8, Canada M5S 1A8. E-mail address: [email protected] ORCID: 0000-0001-7897-4890 (T.H.W.). This work was supported by Canadian Institutes of Health Research (CIHR) Foundation Grant FDN 143250 (to T.H.W.). K.C.W. was funded by a CIHR Canada Graduate Scholarship Masters award and K.-L.C. by an Ontario Graduate Scholarship. T.H.W. holds the Sanofi Pasteur Chair in Human Immunology at the University of Toronto. Abbreviations used in this article: cDC, classical dendritic cell; DC, dendritic cell; IFN-I, type I IFN; InfAPC, inflammatory monocyte-derived APC; LCMV, lymphocytic choriomeningitis; MHC II, MHC class II; pDC, plasmacytoid DC; p.i., postinfection; TG, thioglycolate-elicited. The online version of this article contains supplemental material. This article is distributed under the terms of the CC BY-NC-ND 4.0 Unported license. Copyright © 2018 The Authors https://doi.org/10.4049/immunohorizons.1800047 407 ImmunoHorizons is published by The American Association of Immunologists, Inc. 408 COSTIMULATORY LIGAND EXPRESSION DURING CHRONIC INFECTION ImmunoHorizons Classical dendritic cells (cDC), including dendritic cell (DC) 1 and described (12). A total of 2 3 106 focusformingunitsofLCMV13 DC2, were found to have the highest expression of MHC class II were injected i.v. per mouse where indicated. (MHC II), CD80, and CD86 at day 2 after viral infection, whereas CD64+FceRI+ inflammatory monocyte-derived APC (InfAPC) had Mice low levels of MHC II, CD80, and CD86 but high levels of the TNF Age-matched (6–10 wk old) CD45.2 C57BL/6NCrl female mice family ligands 4-1BBL, GITRL, CD70, and OX40L. Using the GITR were used in all experiments. All animals were housed under costimulatory pathway for proof of concept, we went on to show specific pathogen-free conditions in the Division of Comparative that GITRL on InfAPC provided a postpriming checkpoint, which Medicine at the Terrence Donnelly Centre for Cellular and we called signal 4, that allowed T cells to survive and accumulate to Biomolecular Research (University of Toronto). Animal experi- help control chronic LCMV infection (6). ments were approved by the animal care committee at the Our previous studies of costimulatory ligand expression on University of Toronto in accordance with the Canadian Council on APC subsets during viral infection focused on the first 2 to 3 days of Animal Care (Protocol no. 20011642). infection and on responses to LCMV 13 in the spleen (6). However, T cells can be recruited into an immune response throughout the Abs and reagents course of infection (7). Moreover, APCs are dynamically regulated All Abs and related reagents used in this study are defined in Downloaded from over the course of infection (8, 9), with rapid turnoverof some APC Table I. populations (10). For this reason, it is important to understand APC subset-specific costimulatory molecule expression through to the Flow cytometry chronic phase of infection, as well as to analyze costimulatory Freshly isolated spleens were processed through 70-mm cell molecule expression in the tissues as well as the secondary strainers to create single-cell suspensions. Following perfusion, http://www.immunohorizons.org/ lymphoid organs. Throughout the course of LCMV 13 infection, as lung tissues were first digested with collagenase IV and DNase I for expected, MHC II was found to be consistently higher on cDC 45 min at 37°C on a shaker prior to the use of cell strainers. Lung compared with InfAPC, whereas InfAPC consistently express the tissue was then mechanically disrupted through a 70-mm cell highest levels of TNF family ligands compared with cDC or strainer, and leukocytes were enriched by isolation over an 80/ plasmacytoid DC (pDC) in both the spleen and in the lungs. CD86 40% Percoll gradient (GE healthcare, Chicago, IL) after RBC lysis. was also higher on splenic cDC compared with splenic InfAPC Samples were resuspended in PBS containing 2% FBS and then throughout the infection, whereas CD80 distribution between treated with Fc block for 10 min at 4°C followed by surface staining APC subsets in the spleen varied over the course of the infection. for30minat4°C,exceptfor4-1BBL,CD70,OX40L,andGITRL, TNF family ligands were also preferentially expressed on InfAPC which were stained at room temperature for 30 min between Fc in the lung at day 3 postinfection (p.i.) with LCMV 13. block and the remaining surface staining. Samples from infected by guest on October 3, 2021 Previous results showed that IFN-I coordinately induces all mice were fixed in 4% paraformaldehyde or BD Cytofix Fixation four TNF family ligands, with peak expression at day 2 p.i. in the Buffer following surfacing staining. Data were acquired on a spleen. In this article, we show that there are two patterns of TNF Fortessa X20 or an LSR Fortessa with FACSDiva software. Data family ligand expression at the chronic phase of LCMV infection. analyses were performed using FlowJo v10. Gating strategies are CD70 is induced early during viral infection and then decreases to defined in Supplemental Figs. 1 and 2. at or below baseline within a few days and remains minimally expressed, as previously reported for GITRL (6, 11). In contrast, In vitro thioglycolate-elicited macrophage assays 4-1BBL and OX40L surface expression remain above baseline Mice were injected i.p. with 3% Brewers Thioglycolate medium through the chronic phase of LCMV 13 infection. In vivo, we show aged at room temperature for at least 3 mo.
Load more

Recommended publications
  • Systematic Examination of Antigen-Specific Recall T Cell
    Systematic Examination of Antigen-Specific Recall T Cell Responses to SARS-CoV-2 versus Influenza Virus Reveals a Distinct Inflammatory Profile This information is current as of November 24, 2020. Jaclyn C. Law, Wan Hon Koh, Patrick Budylowski, Jonah Lin, FengYun Yue, Kento T. Abe, Bhavisha Rathod, Melanie Girard, Zhijie Li, James M. Rini, Samira Mubareka, Allison McGeer, Adrienne K. Chan, Anne-Claude Gingras, Tania H. Watts and Mario A. Ostrowski Downloaded from J Immunol published online 18 November 2020 http://www.jimmunol.org/content/early/2020/11/17/jimmun ol.2001067 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2020/11/17/jimmunol.200106 Material 7.DCSupplemental Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on November 24, 2020 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Author Choice Freely available online through The Journal of Immunology Author Choice option Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2020 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published November 18, 2020, doi:10.4049/jimmunol.2001067 The Journal of Immunology Systematic Examination of Antigen-Specific Recall T Cell Responses to SARS-CoV-2 versus Influenza Virus Reveals a Distinct Inflammatory Profile Jaclyn C.
    [Show full text]
  • Dr. Tania Watts
    Interviews Interview with an Immunologist: Dr. Tania Watts Dario M. Ferri and Luke S. Dingwell r. Tania Watts received her After the initial shock dissipated, I started to think Well,“ Ph.D. in Biochemistry from we’re experts in viral immunology, we should do something” - the University of Alberta. She fortunately, I have colleagues in Dr. Mario Ostrowski and Dr. Dthen went on to do a post-doctoral Allison McGeer, both infectious diseases clinician scientists, fellowship at Stanford University so I reached out to them about the possibility of setting up studying T lymphocyte activation, which a project focused on studying human T cell responses to is where she first began to develop her SARS-CoV-2. Once we finalized our idea for the project, passion for immunology. During her there was a bit of a scramble to get all of the necessary post-doctoral work, Dr. Watts helped biosafety approval, but we began our work on SARS-CoV-2 to provide the first evidence for the immunity. I am very fortunate to have an extremely smart existence of a ternary complex existing and hardworking PhD student in Jaclyn Law, who in the between MHC II, peptide antigen, and past few months has had to completely pivot her PhD thesis Dr. Tania Watts the T cell receptor. In 1986, Dr. Watts work towards focusing on SARS-CoV-2 immunity. It was took up a faculty position at the University of Toronto Department also a very active collaboration with members of Mario of Immunology, where her research has been focused on T cell and Ostrowski’s team contributing their assays and expertise as viral immunity.
    [Show full text]
  • And CD137L Responses by Dual Costimulation with CD80
    Enhancement of HIV-Specific CD8 T Cell Responses by Dual Costimulation with CD80 and CD137L This information is current as Jacob Bukczynski, Tao Wen, Chao Wang, Natasha Christie, of September 28, 2021. Jean-Pierre Routy, Mohamed-Rachid Boulassel, Colin M. Kovacs, Kelly S. MacDonald, Mario Ostrowski, Rafick-Pierre Sekaly, Nicole F. Bernard and Tania H. Watts J Immunol 2005; 175:6378-6389; ; doi: 10.4049/jimmunol.175.10.6378 Downloaded from http://www.jimmunol.org/content/175/10/6378 References This article cites 57 articles, 30 of which you can access for free at: http://www.jimmunol.org/content/175/10/6378.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 28, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Enhancement of HIV-Specific CD8 T Cell Responses by Dual Costimulation with CD80 and CD137L1 Jacob Bukczynski,* Tao Wen,2* Chao Wang,* Natasha Christie,* Jean-Pierre Routy,† Mohamed-Rachid Boulassel,† Colin M.
    [Show full text]
  • Imm250h1f “Immunity and Infection” – Fall 2016
    IMM250H1F “IMMUNITY AND INFECTION” – FALL 2016 Students will be introduced to the basic concepts of immunity to infectious disease. We will trace the history of current ideas in immunology by examining how bacteria and viruses cause disease and the initial discoveries that led to such developments as vaccination. Current topical and newsworthy infectious diseases (HIV, Ebola, avian flu, Sepsis) will be used as examples of how the immune system copes with microbial infections and how breakdown of the immune response can lead to diseases such as autoimmunity. IMM250 is a required course for all immunology programs, however it is designed to fulfill breadth requirements and is an appropriate choice for students in other science or humanities programs. Development of writing skills through the composition of a science article for the general public is one objective of this course. Recommended Preparation: BIO120H, BIO130H COURSE DATES AND POLICIES Class time: Tuesdays, 10AM-12noon, Location: OISE Auditorium room G162, 252 Bloor Street. Course coordinator: Dr. Liliana Clemenza [email protected] All postings (lecture material and announcements) will be done on Blackboard. Please check the Portal regularly. Lecturers: Dr. L. Clemenza Office hours: Mondays 12:30-2:30pm, room MSB 7267. Please email in advance for appointment. Other meeting arrangements can be made upon request. Dr. Wendy Tamminen [email protected] Office hours: TBA Guest Lecturers: Dr. Tania Watts Dr. Brian Barber 1 Evaluation Summary and Event Dates: 1. Midterm Test: Weight 20% (multiple-choice questions), it will include the first 5 lectures. When: Tuesday October 11 2016, 11am-12noon (one hour) Location: Exam Centre, rooms: TBA, 255 McCaul Street.
    [Show full text]
  • GITRL on Inflammatory Antigen Presenting Cells in the Lung
    www.nature.com/mi ARTICLE GITRL on inflammatory antigen presenting cells in the lung parenchyma provides signal 4 for T-cell accumulation and tissue-resident memory T-cell formation Kuan-Lun Chu1, Nathalia V. Batista1, Kuan Chung Wang1, Angela C. Zhou1 and Tania H. Watts1 T-cell responses in the lung are critical for protection against respiratory pathogens. TNFR superfamily members play important roles in providing survival signals to T cells during respiratory infections. However, whether these signals take place mainly during priming in the secondary lymphoid organs and/or in the peripheral tissues remains unknown. Here we show that under conditions of competition, GITR provides a T-cell intrinsic advantage to both CD4 and CD8 effector T cells in the lung tissue, as well as for the formation of CD4 and CD8 tissue-resident memory T cells during respiratory influenza infection in mice. In contrast, under non- competitive conditions, GITR has a preferential effect on CD8 over CD4 T cells. The nucleoprotein-specific CD8 T-cell response partially compensated for GITR deficiency by expansion of higher affinity T cells; whereas, the polymerase-specific response was less flexible and more GITR dependent. Following influenza infection, GITR is expressed on lung T cells and GITRL is preferentially expressed on lung monocyte-derived inflammatory antigen presenting cells. Accordingly, we show that GITR+/+ T cells in the lung parenchyma express more phosphorylated-ribosomal protein S6 than their GITR−/− counterparts. Thus, GITR signaling within the lung tissue critically regulates effector and tissue-resident memory T-cell accumulation. Mucosal Immunology (2019) 12:363–377; https://doi.org/10.1038/s41385-018-0105-5 INTRODUCTION checkpoint for CD4 accumulation and shows only indirect effects Influenza remains an important human pathogen.
    [Show full text]
  • October/November 2018
    Department of Immunology Newsletter VOL VII – ISSUE 2 October/November 2018 Message from the Chair, UPCOMING EASTON SEMINARS Dr. Juan Carlos Zúñiga-Pflücker November 2018 With fall fully upon us and with the main MSB 2172 at 11:10 a.m. grant-writing season finally over, it is a good time to start thinking about upcoming events in the Monday, November 5 Department of Immunology. With this in mind, Dr. Graham Pawelec, PhD please note the save the date(s) section. "Interplay between Age, Immunity, Cancer and I am also looking forward to our next departmental CMV" faculty meeting, during which I will provide an Host: Dr. Tania Watts, PhD overview of the next strategic plan for our department. This new plan will be the 2nd Strategic Monday, November 12 Plan for the department, and will build on the many Dr. Alan Sher, PhD successes achieved from our initial strategic plan "Iron Dependent Targets for Host-Directed (2014-2018). In the meantime, we will be Therapy of TB" Host: Dr. David Brooks, PhD conducting interviews and discussion with many of our stakeholders and external advisors to ensure Monday, November 19 our plan reflects areas that still need improvement Dr. Michael Gold, PhD and highlights those that can be further developed. "B Cell Activation in Space and Time" I am also taking this opportunity to say that all look Host: Dr. Robert Rottapel, MD forward to hearing from all of you regarding any new ideas and/or advice that be included as part of Monday, November 26 —No Easton Seminar our new plan.
    [Show full text]
  • A Critical Role for TNF Receptor-Associated Factor 1 and Bim Down-Regulation in CD8 Memory T Cell Survival
    A critical role for TNF receptor-associated factor 1 and Bim down-regulation in CD8 memory T cell survival Laurent Sabbagh*, Cathy C. Srokowski*, Gayle Pulle*, Laura M. Snell*, Bradley J. Sedgmen*, Yuanqing Liu*, Erdyni N. Tsitsikov†, and Tania H. Watts*‡ *Department of Immunology, University of Toronto, 1 King’s College Circle, Toronto, ON, Canada M5S 1A8; and †CBR Institute for Biomedical Research, Harvard Medical School, WAB 124, 200 Longwood Avenue, Boston, MA 02468 Edited by Philippa Marrack, National Jewish Medical and Research Center, Denver, CO, and approved October 16, 2006 (received for review April 10, 2006) The mechanisms that allow the maintenance of immunological involved in the promotion as well as feedback inhibition of TRAF2- memory remain incompletely defined. Here we report that tumor mediated signaling events. necrosis factor receptor (TNFR)-associated factor (TRAF) 1, a protein In T cells, TRAF1 deficiency results in hyperresponsiveness to recruited in response to several costimulatory TNFR family mem- anti-CD3 and TNF stimulation in vitro, suggesting that TRAF1 is bers, is required for maximal CD8 T cell responses to influenza virus a negative regulator of T cell activation (14). In contrast, constitu- in mice. Decreased recovery of CD8 T cells in vivo occurred under tive overexpression of a TRAF1 transgene in a T cell antigen conditions where cell division was unimpaired. In vitro, TRAF1- receptor (TCR) transgenic model led to reduced antigen-induced deficient, antigen-activated T cells accumulated higher levels of the cell death (15). However, the effect of TRAF1 deficiency on proapoptotic BH3-only family member Bim, particularly the most antigen-specific T cell responses in vivo has not yet been analyzed.
    [Show full text]
  • Recent Advances in Immunology IMM1000Y-Syllabus
    Recent Advances in Immunology IMM1000Y Date/Time: Mondays 1:30-4:00pm (unless otherwise specified) Location: Health Science Building – Room 108 155 College Street TORONTO, ON, Canada M5T 1P8 Room 108 is a tentative location reserved for dates that will allow in-person lectures. Under the current circumstances lectures and student presentations will be held in an online, synchronous format (Mondays, 1:30-4:00pm). An invitation to a Zoom meeting will be provided by the course coordinator for each lecture. Note that lectures and student presentations will not be recorded. Course coordinator: Arthur Mortha ([email protected]) Please note that students who are not in the graduate program in Immunology need to obtain prior permission from the course coordinator to register for this course. Prerequisite: The prerequisite for this course is a basic background in Immunology obtained from at least one recent full-year undergraduate course. The course will be taught at a fairly advanced level. Students who are missing background knowledge in some areas should fill the gaps from textbook, discussions with colleagues, or advice from faculty members. Don’t hesitate to reach out. Recommended textbook: Primer to The Immune Response, 2nd Edition. Tak W. Mak, Mary Saunders, and Bradley Jett. 2014 (Academic Press). Evaluation Scheme & Course Assessments: Assessment % of Grade Due Date Midterm Exam 35% December 11, 2020 (4:00pm) Presentation 20% Throughout term Final Exam 45% March 29, 2021 (4:00pm) *All grading will be done by the professor/s who submitted the question or assigned the paper for presentation. The course coordinator will assemble the marks and administer the final mark.
    [Show full text]
  • And Enhance Igg2a Production in Vivo HLA-DM-Sufficient Antigen
    Chemical Chaperones Enhance Superantigen and Conventional Antigen Presentation by HLA-DM-Deficient as well as HLA-DM-Sufficient Antigen-Presenting Cells This information is current as and Enhance IgG2a Production In Vivo of September 24, 2021. Birinder Ghumman, Edward M. Bertram and Tania H. Watts J Immunol 1998; 161:3262-3270; ; http://www.jimmunol.org/content/161/7/3262 Downloaded from References This article cites 44 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/161/7/3262.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 24, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 1998 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Chemical Chaperones Enhance Superantigen and Conventional Antigen Presentation by HLA-DM-Deficient as well as HLA-DM-Sufficient Antigen-Presenting Cells and Enhance IgG2a Production In Vivo1 Birinder Ghumman, Edward M. Bertram, and Tania H. Watts2 Chemical chaperones, first defined in studies of mutant cystic fibrosis transmembrane conductance regulator proteins, are small molecules that act as stabilizers of proteins in their native state and have the ability in some cases to rescue protein-folding mutants within cells.
    [Show full text]
  • L and Bcl-X Staying Alive
    Staying Alive: T Cell Costimulation, CD28, and Bcl-x L Tania H. Watts This information is current as J Immunol 2010; 185:3785-3787; ; of September 25, 2021. doi: 10.4049/jimmunol.1090085 http://www.jimmunol.org/content/185/7/3785 Downloaded from References This article cites 39 articles, 20 of which you can access for free at: http://www.jimmunol.org/content/185/7/3785.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 25, 2021 Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2010 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Staying Alive: T Cell Costimulation, CD28, and Bcl-xL Tania H. Watts he survival of lymphocytes is tightly regulated at each cemented the role of CD28 as a key receptor for signal 2 for stage of their lifespan. Although this may seem ob- T lymphocyte activation (14–19). T vious to us today, prior to the early 1990s, the focus of At the time of the studies of Boise et al.
    [Show full text]
  • 2017-2018 Immunology Seminar Series 12:00 – 1:00 PM, Scaife Auditorium 5 Contact: Jesse Rosenthal, [email protected], 412-648-7050
    2017-2018 Immunology Seminar Series 12:00 – 1:00 PM, Scaife Auditorium 5 Contact: Jesse Rosenthal, [email protected], 412-648-7050 SEPTEMBER 7 – Wajahat Mehal, MD, PhD, Yale University “Sterile Inflammation in the Liver” 14 – Geoffrey Camirand, PhD, University of Pittsburgh “Visualization of Treg suppressor function within non-lymphoid tissues” 21 – NO SEMINAR – Rosh Hoshanah 28 – NO SEMINAR – Department Retreat OCTOBER 5 – EBERLY LECTURE – Klaus Rajewsky, MD, Max Delbruck Center for Molecular Medicine “Signals Controlling Normal and Malignant B Cells” 12 – Charles Drake, MD, PhD, Columbia University “Immunotherapy for GU Cancers” 19 – NO SEMINAR – Science 2017 26 – Shruti Naik, MD, Rockefeller University “Memory of Inflammation in Epidermal Stem Cells” NOVEMBER 2 – Mike Rosenblum, MD, PhD, University of California, San Francisco “Regulatory T Cells in Skin – From Mice to Man” 9 – NO SEMINAR 16 – Robert Lafyatis, MD, University of Pittsburgh “Expansion of pro-fibrotic fibroblasts and macrophages in idiopathic pulmonary fibrosis” 23 – NO SEMINAR – THANKSGIVING 30 – Eugene Oltz, PhD, Washington University in St. Louis “Normal and Pathogenic Regulatory Circuits Governing Gene Expression in Human Lymphoid Cells” DECEMBER 7 – Michael Cancro, PhD, University of Pennsylvania “New subsets, new checkpoints: Expanding roles for Tbet+ B cells in health and disease” 14 – Greg Delgoffe, PhD, University of Pittsburgh 2017-2018 Immunology Seminar Series 12:00 – 1:00 PM, Scaife Auditorium 5 Contact: Jesse Rosenthal, [email protected], 412-648-7050
    [Show full text]
  • Chronic Viral Infection in Mice Ligand Expression on APC Subsets Over
    Conserved and Differential Features of TNF Superfamily Ligand Expression on APC Subsets over the Course of a Chronic Viral Infection in Mice Kuan C. Wang, Kuan-Lun Chu, Nathalia V. Batista and Tania H. Watts Downloaded from ImmunoHorizons 2018, 2 (11) 407-417 doi: https://doi.org/10.4049/immunohorizons.1800047 http://www.immunohorizons.org/content/2/11/407 http://www.immunohorizons.org/ This information is current as of October 6, 2021. Supplementary http://www.immunohorizons.org/content/suppl/2018/12/20/2.11.407.DCSup Material plemental References This article cites 33 articles, 10 of which you can access for free at: http://www.immunohorizons.org/content/2/11/407.full#ref-list-1 Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: by guest on October 6, 2021 http://www.immunohorizons.org/alerts ImmunoHorizons is an open access journal published by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 All rights reserved. ISSN 2573-7732. RESEARCH ARTICLE Infectious Disease Conserved and Differential Features of TNF Superfamily Ligand Expression on APC Subsets over the Course of a Chronic Viral Infection in Mice Kuan C. Wang, Kuan-Lun Chu, Nathalia V. Batista, and Tania H. Watts Downloaded from Department of Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada ABSTRACT http://www.immunohorizons.org/ There is currently much interest in how different APC subsets shape the immune response. We recently described a division of labor between classical dendritic cells (cDC) and inflammatory monocyte-derived APC in provision of costimulatory ligands to T cells early during chronic lymphocytic choriomeningitis clone 13 (LCMV 13) infection in mice.
    [Show full text]