DOCSLIB.ORG

Deciphering Thymic Development

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Deciphering Thymic Development View metadata, citation and similar papers at core.ac.uk brought to you by CORE OPINION ARTICLE published: 08provided October by 2014 Frontiers - Publisher Connector doi: 10.3389/fimmu.2014.00424 Deciphering thymic development Harald Von Boehmer 1,2* 1 Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA 2 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA *Correspondence: [email protected] Edited by: Kendall A. Smith, Weill Medical College of Cornell University, USA Reviewed by: Herman Waldmann, University of Oxford, UK Keywords: MHC-restricted antigen recognition, T cell clones, TCR alpha/beta cDNA clones, HY antigen, TCR transgenic mice, negative thymic selection, positive thymic selection In 1979, some of us were surprised by beta genes from one T cell clone to asked Hans Georg Rammensee who was the (1) conclusion of Doherty and Zinker- another allowed us to unequivocally con- in the same office a related question. I nagel on MHC-restricted antigen recogni- clude that the MHC-restricted specificity leave it to the audience to imagine what tion following the lead of Katz, Hamaoka, was encoded by a single receptor long Michael Steinmetz told Georges Koehler and Benacerraf (2) describing the same before crystallographic studies reached or better what he did not tell him, even for the interaction of T helper cells with the same conclusion (5). This surprised though one cannot be completely sure of B cells as well as Rosenthal and Shevach some molecular biologists somewhat who it. So Georges did not produce the mice (3) describing it for the interaction of T thought that the cloning of the TCR put but Anton Berns in Amsterdam cooper- cells with macrophages. Since Doherty and an end to the mysteries of the immune ated and very nicely mapped what was Zinkernagel offered the least complicated system. required to express TCR beta genes in system, they got most of the credit. We This lead automatically to the next step, transgenic mice. Finally, the co-injection wanted to know whether a single effector the construction of TCR transgenic mice, of alfa and beta genes from an HY spe- cell was involved and therefore analyzed a to analyze the selection of T cells accord- cific clone was done by Horst Bluethmann clone of cells, specific for the HY trans- ing to their specificity. Initially, we were at Hoffmann La Roche in Basel where plantation antigen. If it could be shown interested to test the ideas of Burnet and Michael Steinmetz had moved. When the that the progeny of a single cell was MHC Lederberg that autoaggressive cells were mice had grown up, we tested them with restricted, we had something to explain, eliminated in primary lymphoid organs. a variety of reagents prepared for this which was not obvious. The cloning in For this reason, we used again the genes of task and could report on the deletion of Basel worked fine, with the competent help HY specific clones since then we could eas- CD4C8C cells in male mice even though of Hans Hengartner before his departure ily compare female and male mice. Here, these mice came with an anomaly, the too to the lab of Zinkernagel in Zurich. The I have to tell a little tale that charac- early expression of the transgenic TCR, clone was in fact MHC restricted, telling terizes (some?) scientists: it was Michael which made proper quantitation difficult us that MHC restriction was the property Steinmetz, who had previously spoken to (6). Only recently could we address this of a single cell. The same conclusion was Fritz Melchers, who asked at the Reisens- problem and reported deletion of CD4C8C derived from experiments with Matthias burg in the South of Germany whether thymocytes in the absence of TCR edit- Wabl, who observed the killing of targets there would be any interest in generating ing (7). This ended a long story on the by single killer cell (4). The clone was TCR transgenic mice. I answered with a deletion of autoaggressive cells at a cer- also alloreactive, which was observed prior clear yes saying that this would allow to tain stage of development, something that to the realization that a significant por- test Burnets and Lederbergs ideas. So, it had not been addressed in mice express- tion of T cells carried two receptors and was concluded to go ahead and initially ing superantigen specific receptors, which thus it is unclear to date whether a sec- Georges Koehler was singled out as the somewhat compromised our transgenic ond receptor was involved or not. This was scientist residing by now in Freiburg to approach since they were conducted later just the first example of a clone, which help with the construction of mice since he and yielded results earlier albeit with the was MHC restricted and HY specific as had succeeded to generate immunoglobu- limitation that the conclusions had to be well as H-2Dd specific and this overlap lin transgenic mice. I was therefore mildly restricted to superantigens (8) whereas in specificity was subsequently observed surprised when one day Georges entered we dealt with conventional antigens for in other clones such that the high fre- my lab and asked me whether I could T cells. quency of alloreactive T cells is not really give him an HY specific clone since he The next step was related to positive an issue. had the idea of testing Burnets and Leder- selection and the matching of specificity Follow up experiments with the Michael bergs ideas. I told him that this sounded and function. Here, the first realization was Steinmetz lab transferring TCR alfa and familiar, he blushed only a little and then that a receptor derived from a CD8C cell www.frontiersin.org October 2014 | Volume 5 | Article 424 | 1 Von Boehmer Deciphering thymic development C would only be expressed on CD8 cells questions and think of clever experiments viral peptides. Nature (1989) 340:443–8. doi:10. in the transgenic mice (9, 10). The sec- to address them. 1038/340443a0 ond was that there was in fact positive 13. Deverson EV, Gow IR, Coadwell WJ, Monaco JJ, Butcher GW, Howard JC. MHC class selection as mice with inappropriate MHC REFERENCES II region encoding proteins related to the antigens not restricting the specificity of 1. Zinkernagel RM, Doherty PC. MHC-restricted multidrug resistance family of transmembrane the cell from which receptor genes were cytotoxic T cells: studies on the biological transporters. Nature (1990) 348:738–41. doi:10. obtained, failed to generate single positive role of polymorphic major transplantation 1038/348738a0 cells and thus development was arrested antigens determining T-cell restriction-specificity, 14. Trowsdale J, Hanson I, Mockridge I, Beck S, Townsend A, Kelly A. Sequences encoded in at the CD4C8C stage where cells died (9). function, and responsiveness. Adv Immunol (1979) 27:51–177. doi:10.1016/S0065-2776(08) the class II region of the MHC related to the This was then named death from neglect 60262-X “ABC” superfamily of transporters. Nature (1990) as opposed to death by negative selection 2. Katz DH, Hamaoka T, Benacerraf B. Cell inter- 348:741–4. doi:10.1038/348741a0 which eliminated likewise CD4C8C cells, actions between histoincompatible T and B lym- 15. Monaco JJ, Cho S, Attaya M. Transport protein at least when the receptor was derived from phocytes. II. Failure of physiologic cooperative genes in the murine MHC: possible implications C interactions between T and B lymphocytes from for antigen processing. Science (1990) 250:1723–6. CD8 cells (7). It was then clear that it was allogeneic donor strains in humoral response doi:10.1126/science.2270487 the MHC molecules expressed in the thy- to hapten-protein conjugates. J Exp Med (1973) 16. Spies T, Bresnahan M, Bahram S, Arnold D, mus and the TCR specificity, which deter- 137:1405–18. doi:10.1084/jem.137.6.1405 Blanck G, Mellins E, et al. A gene in the mined positive selection, which also led 3. Rosenthal AS, Shevach EM. Function of human major histocompatibility complex class II region controlling the class I antigen presentation to the matching of specificity and func- macrophages in antigen recognition by guinea C pig T lymphocytes. I. Requirement for histo- pathway. Nature (1990) 348:744–7. doi:10.1038/ tion (10), such that CD8 killer cells were compatible macrophages and lymphocytes. J Exp 348744a0 generated from immature cells express- Med (1973) 138:1194–212. doi:10.1084/jem.138. 17. He X, Park K, Kappes DJ. The role of ThPOK in ing a class I restricted TCR (11) and as 5.1194 control of CD4/CD8 lineage commitment. Annu shown later CD4C helper cells were gen- 4. Wabl MR,von Boehmer H. Single Killer Cells Recog- Rev Immunol (2010) 28:295–320. doi:10.1146/ annurev.immunol.25.022106.141715 erated from immature cells expressing a nize Non-H-2 as well as H-2 Determinants on Target Cells, Annual Report. Basal Institute for Immunol- 18. Egawa T, Littman DR. ThPOK acts late in spec- class II restricted TCR and thus in other ogy (1976), 60 p. ification of the helper T cell lineage and sup- words helper cells recognized as a rule 5. Dembic Z, Haas W, Weiss S, McCubrey J, Kiefer presses Runx-mediated commitment to the cyto- peptides entering the target cell from the H, Boehmer von H, et al. Transfer of specificity toxic T cell lineage. Nat Immunol (2008) 9:1131–9. outside whereas killer cells recognized pep- by murine alpha and beta T-cell receptor genes. doi:10.1038/ni.1652 19. Murata S, Sasaki K, Kishimoto T,Niwa S-I, Hayashi tides produced in the target cell itself.
Load more

Recommended publications
  • Differential Synergy of Notch and T Cell Receptor Signaling Determines Αβ
    ARTICLE Diff erential synergy of Notch and T cell receptor signaling determines αβ versus γδ lineage fate Annette I. Garbe,1 Andreas Krueger,1 Fotini Gounari,1,2 Juan Carlos Zúñiga-Pfl ücker,3 and Harald von Boehmer1 1Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 2Tufts-New England Medical Center, Boston, MA 02111 3University of Toronto, Toronto, Ontario, M4N 3M5 Canada Thymic precursors expressing the pre–T cell receptor (TCR), the TCR, or the TCR can all enter the CD4+8+ lineage, albeit with different effi cacy. Here it is shown that proliferation and differentiation of precursors with the different TCRs into lineage cells require Notch signaling at the DN3 stage of thymic development. At the DN4 stage, Notch signaling still signifi cantly contributes to the generation of T cells. In particular, in lineage commitment, the pre-TCR synergizes more effi ciently with Notch signals than the other two TCRs, whereas TCR-expressing cells can survive and expand in the absence of Notch signals, even though Notch signaling enhances their proliferation. These observations suggest a new model of versus lineage choice in which lineage fate is determined by the extent of synergy between TCR and Notch signaling and in which the evolutionarily recent advent of the cell-autonomously signaling pre-TCR increased the effi cacy of T cell generation. CORRESPONDENCE The mammalian immune system contains sev- essential for the rescue of DP cells from pro- Harald von Boehmer: eral T lymphocyte lineages of which the grammed cell
    [Show full text]
  • Table of Contents
    Cancer Immunology Research Table of Contents July 2014 Volume 2 Issue 7 EDITORIAL RESEARCH ARTICLES 591 Cancer Immunology Research: A One-Year 616 Immunotherapy Converts Nonimmunogenic Anniversary Pancreatic Tumors into Immunogenic Foci of Immune Regulation Eric R. Lutz, Annie A. Wu, Elaine Bigelow, Rajni Sharma, Guanglan Mo, Kevin Soares, Sara Solt, MASTERS OF IMMUNOLOGY Alvin Dorman, Anthony Wamwea, Allison Yager, Daniel Laheru, Christopher L. Wolfgang, 592 The Thymus in Immunity and in Malignancy Jiang Wang, Ralph H. Hruban, Robert A. Anders, Harald von Boehmer Elizabeth M. Jaffee, and Lei Zheng Synopsis: Lutz and colleagues show that an allogeneic vaccine given with or without low-dose cyclophosphamide converted pancreatic cancer into an immunogenic cancer CANCER IMMUNOLOGY AT THE with infiltrating effector lymphocytes and formation of CROSSROADS: EXPERIMENTAL tertiary lymphoid aggregates that are regulatory structures IMMUNOTHERAPIES of adaptive immunity. 632 598 Hostile, Hypoxia–A2-Adenosinergic Tumor Bevacizumab plus Ipilimumab in Patients with Biology as the Next Barrier to Overcome for Metastatic Melanoma Tumor Immunologists F. Stephen Hodi, Donald Lawrence, Cecilia Lezcano, Xinqi Wu, Jun Zhou, Tetsuro Sasada, Wanyong Zeng, Michail V. Sitkovsky, Stephen Hatfield, Anita Giobbie-Hurder, Michael B. Atkins, Robert Abbott, Bryan Belikoff, Dmitriy Lukashev, Nageatte Ibrahim, Philip Friedlander, and Akio Ohta Keith T. Flaherty, George F. Murphy, Scott Rodig, Elsa F. Velazquez, Martin C. Mihm Jr, Sara Russell, MILESTONES IN CANCER
    [Show full text]
  • April 8, 1997, NIH Record, Vol. XLIX, No. 7
    C 0 R a Still The Second Best Thing About Payday Record Debuts on the Web HIGHLIGHTS· From 'Whatchamacallit' to Funshine New Camp Starts for Children The NIH Record, exclusively a paper publication since May 1949, is now Special love Infected with HIV available electronically on the World Wide launches New By Rich McManus Web. It can be accessed within the NIH Camp home page (www.nih.gov) under the nless you just came to NIH a week ago, you probably know at " Information for Employees" and "News Microsoft least something about Camp Fantastic. For the uninitiated, it's and Events" sections. Or open the site Wunderkind ~ a week-long slice of August turned into terrific summer camp directly by going to http://www.nih.gov/ Foretells Future for children-many of them Clinical Center patients-with cancer, news/NIH-Record/archives.htm. and has always been powered by the freehearted and funloving Catch the Record side of the National Cancer Institute-its Pediatric Branch and The Web version is modeled after the on the Web associated caregivers. It began 15 years ago at a 4-H campground paper one and closely resembles it, but has near Front Royal, Va., and has evolved into a year-round, family­ the advantage of color design and centered program that worries not just about the child with photography. The site's opening page is an cancer, but also about the healthy sibling who wonders where all " Archives" of issues that leads off-for the Dyer, Gorgas Talks of mom and dad's attention went.
    [Show full text]
  • Shaping the T Cell Repertoire
    Shaping the T Cell Repertoire Harald von Boehmer J Immunol 2005; 175:7067-7068; ; This information is current as doi: 10.4049/jimmunol.175.11.7067 of September 27, 2021. http://www.jimmunol.org/content/175/11/7067 Downloaded from References This article cites 6 articles, 3 of which you can access for free at: http://www.jimmunol.org/content/175/11/7067.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 27, 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 Errata An erratum has been published regarding this article. Please see next page or: /content/176/1/677.1.full.pdf /content/176/1/677.2.full.pdf 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. Shaping the T Cell Repertoire Harald von Boehmer1 Today immunologists are well aware of positive to self. In this hypothesis, the focus on self-MHC was imposed and negative selection of developing T cells.
    [Show full text]
  • Harald Von Boehmer 1942–2018
    obituary Harald von Boehmer 1942–2018 oday, few topics in immunology Notch family of signaling receptors in this receive more attention than efforts malignancy. With colleagues in the lab, Tto detect, induce or reinvigorate the Harald also published important insights immune response to tumors. Although into the mechanisms through which many types of immune cells affect different T cell populations respond to and contribute to anti-tumor immune tumors and destroy pancreatic β -cells. At responses, the initial clinical findings that the same time, he never stopped pursuing electrified the field focused on the T cell. knowledge of the basic mechanisms that Cancer biologists who grabbed the nearest affect T cell development. While in Boston, immunology textbook in an effort to fully his lab described mechanisms that affect comprehend and build upon those initial the development of regulatory T cells in the clinical successes will have quickly realized thymus and the periphery and continued that at their core, such approaches rely on to publish insights into the structure and understanding how T cells recognize and function of the pre-TCR. respond to antigen. What they may not After closing his Boston lab, Harald have realized is how important Harald returned to his alma mater as a guest von Boehmer’s work was in laying the professor at the Institute for Immunology foundation for this understanding. of the Ludwig Maximilian University in Long before translational research was Munich. In his writings during this period, all the rage, Harald charged a segment of between the TCR and peptide–major Harald expressed optimism about the future his lab with investigating how fundamental histocompatibility complex determined of immunological research.
    [Show full text]
  • Deciphering Thymic Development
    Deciphering Thymic Development The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Von Boehmer, Harald. 2014. “Deciphering Thymic Development.” Frontiers in Immunology 5 (1): 424. doi:10.3389/fimmu.2014.00424. http://dx.doi.org/10.3389/fimmu.2014.00424. Published Version doi:10.3389/fimmu.2014.00424 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:13347532 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA OPINION ARTICLE published: 08 October 2014 doi: 10.3389/fimmu.2014.00424 Deciphering thymic development Harald Von Boehmer 1,2* 1 Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA 2 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA, USA *Correspondence: [email protected] Edited by: Kendall A. Smith, Weill Medical College of Cornell University, USA Reviewed by: Herman Waldmann, University of Oxford, UK Keywords: MHC-restricted antigen recognition, T cell clones, TCR alpha/beta cDNA clones, HY antigen, TCR transgenic mice, negative thymic selection, positive thymic selection In 1979, some of us were surprised by beta genes from one T cell clone to asked Hans Georg Rammensee who was the (1) conclusion of Doherty and Zinker- another allowed us to unequivocally con- in the same office a related question. I nagel on MHC-restricted antigen recogni- clude that the MHC-restricted specificity leave it to the audience to imagine what tion following the lead of Katz, Hamaoka, was encoded by a single receptor long Michael Steinmetz told Georges Koehler and Benacerraf (2) describing the same before crystallographic studies reached or better what he did not tell him, even for the interaction of T helper cells with the same conclusion (5).
    [Show full text]
  • The Henry Kunkel Society Annual Meeting: Infectious Disease Susceptibility and the Expanding Universe of Primary Immunodeficiency
    The Henry Kunkel Society Annual Meeting: Infectious Disease Susceptibility and the Expanding Universe of Primary Immunodeficiency The Rockefeller University New York, NY April 17–20, 2013 Henry George Kunkel 1916–1983 enry Kunkel received his B.S. degree from Princeton and his M.D. degree from Johns Hopkins University. He arrived at The Rockefeller Institute (now University) in 1945 where he spent his entire scientific career H until his death in 1983. His contributions to the field of basic and clinical immunology are legendary. He made numerous seminal observations in liver disease, rheumatic diseases and other allied disorders. He was perhaps best known for his pioneering and extensive studies on the immunoglobulins. His recognition that myeloma proteins were a model for the study of the structure of normal immunoglobulins had a global impact on investigations of the structure, function and inheritance of these molecules. The elucidation of the chain structure of gamma globulin and the recognition that immunoglobulins possessed individual antigenic specificity (idiotypes) were internationally recognized discoveries. Dr. Kunkel was the recipient of many awards and honors, including membership in the National Academy of Sciences, honorary degrees from Universities of Uppsala and Harvard, and recipient of the Lasker and Gairdner Awards and the Kovalenko Medal of the National Academy of Sciences. Henry Kunkel Society Officers Henry Kunkel Society Lecturers President ................Westley Reeves 1992. Louis Kunkel 2003. .Fred Rosen Vice President ...............Keith Elkon 1993. .David Ho 2004. .Diane Mathis Secretary ........... Michel Nussenzweig 1994. Benvenuto Pernis 2005. Charles Weissman Treasurer ...............Anne Marshak- 1996. Jeffrey Ravetch 2006. Ralph M. Steinman Rothstein 1997. Anthony Fauci 2007.
    [Show full text]
  • The Paul Ehrlich Foundation
    The Paul Ehrlich Foundation Office of the Paul Ehrlich Foundation Contents Paul Ehrlich-Stiftung c/o Vereinigung von Freunden und Förderern der Goethe-Universität Theodor-W.-Adorno-Platz 1 Preface 5 60629 Frankfurt am Main E-Mail: [email protected] www.paul-ehrlich-stiftung.de Paul Ehrlich: His Life March 2021 and Achievements 6 Ludwig Darmstaedter: Donation account: Scientist and Friend 12 Deutsche Bank AG IBAN: DE38 5007 0010 0700 0839 00 BIC: DEUTDEFFXXX The Foundation, the Prize and the Role of Hedwig Ehrlich 14 The Paul Ehrlich and Ludwig Darmstaedter Prize for Young Researchers 17 Preface In honor of the great German doctor and Paul Ehrlich, like all great researchers, was serologist who turned Frankfurt into a way ahead of his time. His research work medical eldorado at the beginning of the laid the cornerstone for the medical stand- 20th century, the Paul Ehrlich and Ludwig ards still valid today. In awarding the Paul Darmstaedter Prize is awarded to scientists Ehrlich and Ludwig Darmstaedter Prize, the from all over the world who have achieved Foundation wishes to encourage scientists all outstanding results in Paul Ehrlich’s field over the world to do what Paul Ehrlich did of work. throughout his entire life: extend medical know-how and make a contribution to the The prize given by the Paul Ehrlich constant struggle against illness and disease- Foundation is one of Germany’s most emi- induced mortality. nent accolades in recognition of outstand- ing achievements in biomedical research. The President of the German Research Foundation (DFG) is Honorary President of the Paul Ehrlich Foundation.
    [Show full text]
  • Immunology in Germany German Society for Immunology
    1901 1984 Emil von Behring Georges J.F. Köhler Nobelprize ‘for his work on serum Nobelprize therapy, especially its ‘for theories application against concerning the diphtheria, by which specificity in 2008 he has opened a new 1905 development and Harald zur road in the domain of Robert Koch control of the Hausen medical science and 1908 immune system thereby placed in the Nobelprize Paul Ehrlich and the discovery Nobelprize hands of the physician ‘for his investigations of the principle ‘for his discovery of a victorious weapon and discoveries in Nobelprize for production human papilloma against illness and relation to ‘in recognition of his of monoclonal viruses causing deaths’ tuberculosis’ work on immunity’ antibodies’ cervical cancer’ Immunology in Germany German Society for Immunology Content Preface ............................................................................... 3 About the DGfI ...................................................................4 Academy of Immunology ...................................................6 Research Focus Groups ......................................................7 Scientific Awards ................................................................8 Annual Meeting ...............................................................10 International Networks & Bilateral Meetings ..................11 Immunology in Germany - Overview ..............................12 Public Outreach - ‚Immunology for Everyone‘ ................16 Membership in the DGfI? Yes! .........................................17
    [Show full text]
  • How Does the Immune System Learn to Distinguish Between Good and Evil? the First Definitive Studies of T Cell Central Tolerance and Positive Selection
    Immunogenetics (2019) 71:513–518 https://doi.org/10.1007/s00251-019-01127-8 REVIEW How does the immune system learn to distinguish between good and evil? The first definitive studies of T cell central tolerance and positive selection Paweł Kisielow1 Received: 30 July 2019 /Accepted: 3 August 2019/Published online: 15 August 2019 # The Author(s) 2019 Abstract Demonstration that immature CD4 + 8+ thymocytes contain T cell precursors that are subjected to positive and negative selection was the major step towards understanding how the adaptive immune system acquires the ability to distinguish foreign or abnormal (mutated or infected) self-cells from normal (healthy) cells. In the present review, the roles of TCR, CD4, CD8, and MHC molecules in intrathymic selection and some of the crucial experiments that contributed to the solution of the great immunological puzzle of self/ nonself discrimination are described in an historical perspective. Recently, these experiments were highlighted by the immunological community by awarding the 2016 Novartis Prize for Immunology to Philippa Marrack, John Kappler, and Harald von Boehmer. Keywords Tcells . Positive and negative selection . Self/nonself discrimination Introduction 1959; Peter Medawar, 1960; Gerald Edelman and Roney Porter, 1972; Baruj Benaceraff, Jean Dausset, and George The “Good” that is protected by the immune system consists Snell, 1983; Niels Jerne, George Koehler, and Cesar Milstein of properly functioning healthy cells, and the “Evil” that is 1984; Susumu Tonegawa, 1987; Peter Doherty
    [Show full text]
  • Table of Contents (PDF)
    Cancer Immunology Research Table of Contents July 2014 Volume 2 Issue 7 EDITORIAL RESEARCH ARTICLES 591 Cancer Immunology Research: A One-Year 616 Immunotherapy Converts Nonimmunogenic Anniversary Pancreatic Tumors into Immunogenic Foci of Immune Regulation Eric R. Lutz, Annie A. Wu, Elaine Bigelow, Rajni Sharma, Guanglan Mo, Kevin Soares, Sara Solt, MASTERS OF IMMUNOLOGY Alvin Dorman, Anthony Wamwea, Allison Yager, Daniel Laheru, Christopher L. Wolfgang, 592 The Thymus in Immunity and in Malignancy Jiang Wang, Ralph H. Hruban, Robert A. Anders, Harald von Boehmer Elizabeth M. Jaffee, and Lei Zheng Synopsis: Lutz and colleagues show that an allogeneic vaccine given with or without low-dose cyclophosphamide converted pancreatic cancer into an immunogenic cancer CANCER IMMUNOLOGY AT THE with infiltrating effector lymphocytes and formation of CROSSROADS: EXPERIMENTAL tertiary lymphoid aggregates that are regulatory structures IMMUNOTHERAPIES of adaptive immunity. 632 598 Hostile, Hypoxia–A2-Adenosinergic Tumor Bevacizumab plus Ipilimumab in Patients with Biology as the Next Barrier to Overcome for Metastatic Melanoma Tumor Immunologists F. Stephen Hodi, Donald Lawrence, Cecilia Lezcano, Xinqi Wu, Jun Zhou, Tetsuro Sasada, Wanyong Zeng, Michail V. Sitkovsky, Stephen Hatfield, Anita Giobbie-Hurder, Michael B. Atkins, Robert Abbott, Bryan Belikoff, Dmitriy Lukashev, Nageatte Ibrahim, Philip Friedlander, and Akio Ohta Keith T. Flaherty, George F. Murphy, Scott Rodig, Elsa F. Velazquez, Martin C. Mihm Jr, Sara Russell, MILESTONES IN CANCER
    [Show full text]
  • Shaping the T Cell Repertoire Harald Von Boehmer J Immunol 2006; 176:3-4; ; This Information Is Current As Doi: 10.4049/Jimmunol.176.1.3 of September 28, 2021
    Shaping the T Cell Repertoire Harald von Boehmer J Immunol 2006; 176:3-4; ; This information is current as doi: 10.4049/jimmunol.176.1.3 of September 28, 2021. http://www.jimmunol.org/content/176/1/3 Downloaded from References This article cites 6 articles, 2 of which you can access for free at: http://www.jimmunol.org/content/176/1/3.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 28, 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 © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Shaping the T Cell Repertoire1 Harald von Boehmer2 Today immunologists are well aware of positive lected by self-MHC molecules in the thymus would proliferate and negative selection of developing T cells. This and mutate their receptors such that they would preferentially was very different almost three decades ago when recognize “altered-self” MHC molecules, which were “similar” MHC-restricted Ag recognition by T cells repre- to self.
    [Show full text]