DOCSLIB.ORG

T-Cell Tolerance: Central and Peripheral

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
T-Cell Tolerance: Central and Peripheral Downloaded from http://cshperspectives.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press T-Cell Tolerance: Central and Peripheral Yan Xing and Kristin A. Hogquist Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455 Correspondence: [email protected] Somatic recombination of TCR genes in immature thymocytes results in some cellswith useful TCR specificities, but also many with useless or potentially self-reactive specificities. Thus thymic selection mechanisms operate to shape the T-cell repertoire. Thymocytes that have a TCR with low affinity for self-peptide–MHC complexes are positively selected to further differentiate and function in adaptive immunity, whereas useless ones die by neglect. Clonal deletion and clonal diversion (Treg differentiation) are the major processes in the thymus that eliminate or control self-reactive T cells. Although these processes are thought to be efficient, they fail to control self-reactivity in all circumstances. Thus, peripheral toler- ance processes exist wherein self-reactive T cells become functionally unresponsive (anergy) or are deleted after encountering self-antigens outside of the thymus. Recent advances in mechanistic studies of central and peripheral T-celltolerance are promoting the development of therapeutic strategies to treat autoimmune disease and cancer and improve transplantation outcome. cells recognize pathogen fragments in the However, not all antigens that T cells need to be Tcontext of surface MHC molecules on host tolerant of are expressed in the thymus, and thus cells. As such, they have the potential to do enor- central tolerance mechanisms alone are insuffi- mous damage to healthy tissue when they are cient. Fortunately, additional tolerance mech- not appropriately directed, that is, when they anisms exist that restrain the numbers and or respond to self-antigens as opposed to foreign function of T cells that are reactive to develop- antigens. T lymphocyte tolerance is particularly mental or food antigens, which are not thymi- important, because it impacts B-cell tolerance as cally expressed. These mechanisms act on ma- well, through the requirement of T cell help in ture circulating T cells and are referred to as antibody responses. Thus, failure of T-cell tol- “peripheral tolerance.” erance can lead to many different autoimmune diseases. The tolerance of T cells begins as soon CENTRAL TOLERANCE as a T-cell receptor is formed and expressed on the cell surface of a T-cell progenitor in the thy- T lymphocytes arise from circulating bone-mar- mus. Tolerance mechanisms that operate in the row-derived progenitors that home to the thy- thymus before the maturation and circulation mus. After T lineage commitment and expan- of T cells are referred to as “central tolerance.” sion, T-cell receptor (TCR) gene rearrangement Editors: Diane J. Mathis and Alexander Y. Rudensky Additional Perspectives on Immune Tolerance available at www.cshperspectives.org Copyright # 2012 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a006957 Cite this article as Cold Spring Harb Perspect Biol 2012;4:a006957 1 Downloaded from http://cshperspectives.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Y. Xing and K.A. Hogquist ensues and gives rise to either gd or ab progen- dergoing secondary gene rearrangement at the itors at the CD4 and CD8 double-negative (DN) TCRa loci, thereby changing the specificity of stage. A small number of ab committed DN the TCR. This process is known as “receptor cells give rise to a large number of CD4 and editing.” Although examples of receptor editing CD8 double-positive (DP) thymocytes, and so- exist for T cells (Wanget al. 1998; McGargill et al. matic recombination of TCR genes results in 2000, 2002; Buch et al. 2002; Santori et al. 2002), a remarkably broad repertoire of distinct ab it is unclear how prominent this mechanism TCRs with random specificity. The TCR affinity is (Holman et al. 2003), and it will not be dis- for self-peptide–major histocompatibilitycom- cussed further here. Finally, a state of unrespon- plex (MHC) determines a thymocyte’s fate from siveness can be induced in self-reactive thymo- this point forward (Fig. 1). DP thymocytes ex- cytes, called “anergy.” Anergy is likely a more pressing TCRs that do not bind self-peptide– prominent tolerance mechanism that operates MHC complexes die by neglect. Those with a in the periphery and is discussed further in low affinity for self-peptide–major histocom- that section. These four processes—clonal dele- patibility complex MHC complexes differenti- tion, clonal diversion, receptor editing, and an- ate to CD4 or CD8 single-positive (SP) thymo- ergy—are the major mechanisms that limit the cytes—so-called positive selection. However, self-reactivity of the T-cell repertoire and are those with high-affinity TCR for self-peptide– crucial for immune health. MHC complexes represent a potential threat to the health of the animal, and various mecha- CLONAL DELETION nisms operate to ensure tolerance to self, includ- ing clonal deletion, clonal diversion, receptor In this section, we discuss several fundamental editing, and anergy. questions of clonal deletion, such as: At which In the thymus, one of the main mechanisms stages of development do thymocytes undergo of T-cell tolerance is “clonal deletion,” although deletion? Where does it occur anatomically? the selection of regulatory T cells (“clonal diver- What cell types induce apoptosis? What is the sion”) is also important and is of enormous in- molecular mechanism? terest (see Benoist 2012). Thymocytes express- The thymus is composed of two major an- ing high-affinity TCR for self-peptide–MHC atomical areas—an outer region known as the can avoid the deletion or diversion fates via un- cortex, which contains DN and DP thymocytes, Death Cells Clonal by Positive deletion neglect selection Treg TCR affinity Figure 1. A model for the relationship between developmental outcome and TCR affinity for self-peptide– MHC. Cells with TCR that have a low affinity for self die by neglect. Those with an intermediate affinity are positively selected. High-affinity self-reactive clones can die via clonal deletion, and the threshold between positive and negative selection is hypothesized to be steep. Regulatory T cells (Treg) (yellow) have more highly self-reactive TCRs than most conventional T cells (purple). Some Tregs may have very highly self-reactive TCRs and are rescued from deletion via cytokine signaling or by virtue of having a second TCR (dotted line). 2 Cite this article as Cold Spring Harb Perspect Biol 2012;4:a006957 Downloaded from http://cshperspectives.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press T-Cell Tolerance and an inner region known as the medulla, tified by the observation that superantigens are which contains SP thymocytes (Fig. 2). Positive primarily expressed in the medulla, which is the selection of thymocytes occurs in the cortex. site where SP thymocytes reside. Likewise, tis- However, whether or not clonal deletion occurs sue-specific antigens are often expressed exclu- in the cortex has been controversial. For exam- sively in the medulla (see below for further dis- ple, superantigen studies have suggested that cussion). In contrast, in TCR transgenic models deletion occurs at the SP stage (Kappler et al. where the TCR is specific for ubiquitous self- 1987) (in the thymic medulla), whereas exam- antigens, deletion occurs at the DN-to-DP tran- ination of TCR transgenics and endogenous sition. However, in transgenic models, thymo- self-antigens had suggested that deletion occurs cytes express both TCRb and TCRa chains early at the transition from DN to DP (Kisielow et al. at the DN stage and undergo negative selection 1988; Sha et al. 1988) (in the thymic cortex). prematurely (Baldwin et al. 2005; Egawa et al. This apparent discrepancy can be partially rec- 2008). What is clear is that the nature of TCR Positive selection, neglect, and clonal deletion Clonal deletion and Treg differentiation Apoptosis Cortex Medulla (neglect) Treg SP Apoptosis DP (deletion) Apoptosis (deletion) DC DC cTEC mTEC CD28 CD4 DP SP CD4 or CD8 B7 TCR or CD8 CD40L p-MHC TCR RANKL β5i p-MHC LT CD40 Ctss RANK β5t AIRE TSSP LT-βR TSAs B7 Ctsl B7 p-MHC p-MHC CD40 CD40 DC cTEC DC mTEC Figure 2. Cell types in central tolerance. (Top) T cells are positively selected in the thymic cortex. Negative selection via clonal deletion can also occur in the cortex, but occurs frequently in the medulla. The thymic medulla is also the site for Treg differentiation. (Bottom) Cortical thymic epithelial cells (cTECs) express several unique genes that relate to proteolysis (cathepsin L, Ctsl; thymus-specific serine protease, TSSP; and b-5t proteasome subunit, b5t), which are essential for positive selection. Tissue-specific antigens (TSAs) can be directly presented by medullary thymic epithelial cells (mTECs) or cross-presented by DC (dotted line with arrow). RANKL, CD40L, and lymphotoxin (LT) expressed by SP thymocytes interact with their receptors on mTEC to promote the development of mTEC. Cite this article as Cold Spring Harb Perspect Biol 2012;4:a006957 3 Downloaded from http://cshperspectives.cshlp.org/ on September 24, 2021 - Published by Cold Spring Harbor Laboratory Press Y. Xing and K.A. Hogquist and self-antigen expression can dramatically trophy syndrome (APECED) (Anderson and impact the
Load more

Recommended publications
  • B Cell Activation and Escape of Tolerance Checkpoints: Recent Insights from Studying Autoreactive B Cells
    cells Review B Cell Activation and Escape of Tolerance Checkpoints: Recent Insights from Studying Autoreactive B Cells Carlo G. Bonasia 1 , Wayel H. Abdulahad 1,2 , Abraham Rutgers 1, Peter Heeringa 2 and Nicolaas A. Bos 1,* 1 Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, 9713 Groningen, GZ, The Netherlands; [email protected] (C.G.B.); [email protected] (W.H.A.); [email protected] (A.R.) 2 Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 Groningen, GZ, The Netherlands; [email protected] * Correspondence: [email protected] Abstract: Autoreactive B cells are key drivers of pathogenic processes in autoimmune diseases by the production of autoantibodies, secretion of cytokines, and presentation of autoantigens to T cells. However, the mechanisms that underlie the development of autoreactive B cells are not well understood. Here, we review recent studies leveraging novel techniques to identify and characterize (auto)antigen-specific B cells. The insights gained from such studies pertaining to the mechanisms involved in the escape of tolerance checkpoints and the activation of autoreactive B cells are discussed. Citation: Bonasia, C.G.; Abdulahad, W.H.; Rutgers, A.; Heeringa, P.; Bos, In addition, we briefly highlight potential therapeutic strategies to target and eliminate autoreactive N.A. B Cell Activation and Escape of B cells in autoimmune diseases. Tolerance Checkpoints: Recent Insights from Studying Autoreactive Keywords: autoimmune diseases; B cells; autoreactive B cells; tolerance B Cells. Cells 2021, 10, 1190. https:// doi.org/10.3390/cells10051190 Academic Editor: Juan Pablo de 1.
    [Show full text]
  • Pathway in the Thymus by a CD24-Dependent Autoreactive T
    Autoreactive T Cells Escape Clonal Deletion in the Thymus by a CD24-Dependent Pathway This information is current as Joseph W. Carl, Jr., Jin-Qing Liu, Pramod S. Joshi, Hani Y. of September 27, 2021. El-Omrani, Lijie Yin, Xincheng Zheng, Caroline C. Whitacre, Yang Liu and Xue-Feng Bai J Immunol 2008; 181:320-328; ; doi: 10.4049/jimmunol.181.1.320 http://www.jimmunol.org/content/181/1/320 Downloaded from References This article cites 54 articles, 18 of which you can access for free at: http://www.jimmunol.org/content/181/1/320.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 27, 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 © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Autoreactive T Cells Escape Clonal Deletion in the Thymus by a CD24-Dependent Pathway1 Joseph W. Carl, Jr.,* Jin-Qing Liu,* Pramod S.
    [Show full text]
  • Natural Killer T Cells Are Required for the Development of a Superantigen-Driven T Helper Type 2 Immune Response in Mice
    IMMUNOLOGY ORIGINAL ARTICLE Natural killer T cells are required for the development of a superantigen-driven T helper type 2 immune response in mice Auro Nomizo,1 Edilberto Postol,2 Summary Raquel de Alencar,2 Fabı´ola We show, here, that one single injection or weekly injections of staphylo- Cardillo2 and Jose´ Mengel2 coccal enterotoxin B (SEB), starting in 1-day-old newborn mice, induced 1Department of Clinical Analysis, Toxicology a powerful immune response with a T helper type 2 (Th2) pattern, as and Bromatology, Faculty of Pharmaceutical Sciences of Ribeira˜o Preto, University of Sa˜o judged by the isotype and cytokine profile, with the production of large Paulo, Ribeira˜o Preto, and 2Department of amounts of SEB-specific immunoglobulin G1 (IgG1), detectable levels of Immunology, Institute of Biomedical Sciences, SEB-specific IgE and increased production of interleukin-4 by spleen cells. University of Sa˜o Paulo, Sa˜o Paulo, SP, Brazil These protocols also induced an increase in the levels of total IgE in the serum. Memory of SEB was transferred to secondary recipients by using total spleen cells from primed animals. The secondary humoral response in transferred mice was diminished if spleen cells from SEB-treated mice were previously depleted of CD3+ or Vb8+ T cells or NK1.1+ cells. In vivo depletion of NK1.1+ cells in adult mice resulted in a marked reduction in the SEB-specific antibody response in both the primary and secondary doi:10.1111/j.1365-2567.2005.02215.x immune responses. Additionally, purified NK1.1+ T cells were able to per- Received 11 April 2005; revised 23 May 2005; form SEB-specific helper B-cell actions in vitro and in vivo.
    [Show full text]
  • Of T Cell Tolerance
    cells Review Strength and Numbers: The Role of Affinity and Avidity in the ‘Quality’ of T Cell Tolerance Sébastien This 1,2,† , Stefanie F. Valbon 1,2,†, Marie-Ève Lebel 1 and Heather J. Melichar 1,3,* 1 Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, Canada; [email protected] (S.T.); [email protected] (S.F.V.); [email protected] (M.-È.L.) 2 Département de Microbiologie, Immunologie et Infectiologie, Université de Montréal, Montréal, QC H3C 3J7, Canada 3 Département de Médecine, Université de Montréal, Montréal, QC H3T 1J4, Canada * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: The ability of T cells to identify foreign antigens and mount an efficient immune response while limiting activation upon recognition of self and self-associated peptides is critical. Multiple tolerance mechanisms work in concert to prevent the generation and activation of self-reactive T cells. T cell tolerance is tightly regulated, as defects in these processes can lead to devastating disease; a wide variety of autoimmune diseases and, more recently, adverse immune-related events associated with checkpoint blockade immunotherapy have been linked to a breakdown in T cell tolerance. The quantity and quality of antigen receptor signaling depend on a variety of parameters that include T cell receptor affinity and avidity for peptide. Autoreactive T cell fate choices (e.g., deletion, anergy, regulatory T cell development) are highly dependent on the strength of T cell receptor interactions with self-peptide. However, less is known about how differences in the strength Citation: This, S.; Valbon, S.F.; Lebel, of T cell receptor signaling during differentiation influences the ‘function’ and persistence of anergic M.-È.; Melichar, H.J.
    [Show full text]
  • B Lymphocytes in Neuromyelitis Optica
    VIEWS & REVIEWS B lymphocytes in neuromyelitis optica Jeffrey L. Bennett, MD, ABSTRACT PhD Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the CNS that predomi- ’ Kevin C. O Connor, PhD nantly affects the spinal cord and optic nerves. A majority (approximately 75%) of patients with Amit Bar-Or, MD, FRCP NMO are seropositive for autoantibodies against the astrocyte water channel aquaporin-4 Scott S. Zamvil, MD, (AQP4). These autoantibodies are predominantly IgG1, and considerable evidence supports their PhD pathogenicity, presumably by binding to AQP4 on CNS astrocytes, resulting in astrocyte injury Bernhard Hemmer, MD and inflammation. Convergent clinical and laboratory-based investigations have indicated that Thomas F. Tedder, PhD B cells play a fundamental role in NMO immunopathology. Multiple mechanisms have been H.-Christian von hypothesized: AQP4 autoantibody production, enhanced proinflammatory B cell and plasmablast Büdingen, MD activity, aberrant B cell tolerance checkpoints, diminished B cell regulatory function, and loss of Olaf Stuve, MD, PhD B cell anergy. Accordingly, many current off-label therapies for NMO deplete B cells or modulate Michael R. Yeaman, PhD their activity. Understanding the role and mechanisms whereby B cells contribute to initiation, Terry J. Smith, MD maintenance, and propagation of disease activity is important to advancing our understanding Christine Stadelmann, of NMO pathogenesis and developing effective disease-specific therapies. Neurol Neuroimmunol MD Neuroinflamm 2015;2:e104;
    [Show full text]
  • Proapoptotic Protein Bim Is Differentially Required During Thymic Clonal Deletion to Ubiquitous Versus Tissue-Restricted Antigens
    Proapoptotic protein Bim is differentially required during thymic clonal deletion to ubiquitous versus tissue-restricted antigens Alexander Y. W. Suen and Troy A. Baldwin1 Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada T6G 2S2 Edited by Michael J. Bevan, University of Washington, Seattle, WA, and approved December 8, 2011 (received for review September 8, 2011) Positive and negative selection of thymocytes in the thymus are positively selected by high-affinity antigen encounter in the thy- critical for the development of a mature and self-tolerant T-cell mus (6). One such example are T-regulatory (Treg) cells, which repertoire. The proapoptotic Bcl-2 family member Bim is important are believed to require high-affinity interactions to develop in the for negative selection by inducing apoptosis in thymocytes receiv- medulla (7). It remains unknown what drives this distinction ing a strong signal through their antigen receptor. However, in the between negative selection and Treg development, although case of ubiquitous self-antigens (UbA), Bim is not required for the secondary signals, such as TGF-β, may play a role in overcoming clonal deletion of self-reactive thymocytes, suggesting the exis- cell death (8). tence of nonapoptotic clonal deletion mechanisms. Unlike UbA, Although it is unclear how the same TCR can transduce a sig- clonal deletion to tissue-restricted antigens (TRAs) requires posi- nal for positive or negative selection, differential mitogen-acti- tive selection and CCR7-mediated migration to the medulla. This vated protein kinase signaling appears to play a role, ultimately led us to hypothesize that Bim is required for the latter.
    [Show full text]
  • Prenatal Allospecific NK Cell Tolerance Hinges on Instructive
    Prenatal Allospecific NK Cell Tolerance Hinges on Instructive Allorecognition through the Activating Receptor during Development This information is current as of September 23, 2021. Amir M. Alhajjat, Beverly S. Strong, Amanda E. Lee, Lucas E. Turner, Ram K. Wadhwani, John R. Ortaldo, Jonathan W. Heusel and Aimen F. Shaaban J Immunol 2015; 195:1506-1516; Prepublished online 1 July 2015; Downloaded from doi: 10.4049/jimmunol.1500463 http://www.jimmunol.org/content/195/4/1506 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2015/07/01/jimmunol.150046 Material 3.DCSupplemental References This article cites 45 articles, 24 of which you can access for free at: http://www.jimmunol.org/content/195/4/1506.full#ref-list-1 Why The JI? Submit online. by guest on September 23, 2021 • 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 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 © 2015 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Prenatal Allospecific NK Cell Tolerance Hinges on Instructive Allorecognition through the Activating Receptor during Development Amir M.
    [Show full text]
  • T-Cell Tolerance by Prof. Anand Prakash
    PROF. ANAND PRAKASH Department of Biotechnology Mahatma Gandhi Central University Motihari Bihar • Immature T-Cells enter in the thymus after differentiating in the bone marrow. • These T-cells undergo maturation and develop TCRs through Somatic Recombination. Bone Marrow Precursors of the T-Cells enter from Bone marrow to THYMUS thymus T Cell Maturation starts Expression of TCR s • DEVELOPMENT OF T-CELL RECEPTORS (TCRs) Some of T-Cells in the thymus develop receptors which are useless with no antigen specificity and while others develop TCRs with • specificity for self antigens and non-self antigens. Thymocytes having TCRs with low affinity for auto antigens, displayed in the MHC class I and II, undergo positive selection and further differentiate to become part of adaptive immunity, whereas the one with non-functional receptors die off because of • negligence. Clonal deletion of T-cells with useless TCRs and high affinity receptors along with clonal diversion for development of “Treg”, are the major processes operative in the thymus towards elimination or regulation of self-reactive T cells. INSIDE THE THYMUS THE T-CELLS UNDERGO AN ELABORATE SCREENING PROCEDURE3 THROUGH FOLLOWING MECHANISMS • • • T CELLS RECOGNIZE ANTIGEN DERIVED PEPTIDES PRESENTED BY MHC MOLECULES MHC Class II MHC Class I Antigen Infected or Presenting Tumour Cell Cell CD8 Peptide CD4 CD4+ CD8+ Helper Cell Cytotoxic T Cell T Cell Receptor T Cell Receptor T CELLS RECOGNIZE ANTIGEN DERIVED PEPTIDES PRESENTED BY MHC MOLECULES Inside Thymus THYMIC T -CELL FATE IS DETERMINED BY STRENGTH OF TCR-MHC/PEPTIDE INTERACTION Thymic MHC stromal Cell Thymic T Cell TCR + CD4 CD8 • NEGATIVE SELECTION Negative selection occurs at the Double positive stage in the thymic cortex, or at the Single Positive stage in the thymic medulla.
    [Show full text]
  • The Importance of Dendritic Cells in Maintaining Immune Tolerance Cindy Audiger, M
    The Importance of Dendritic Cells in Maintaining Immune Tolerance Cindy Audiger, M. Jubayer Rahman, Tae Jin Yun, Kristin V. Tarbell and Sylvie Lesage This information is current as of October 1, 2021. J Immunol 2017; 198:2223-2231; ; doi: 10.4049/jimmunol.1601629 http://www.jimmunol.org/content/198/6/2223 Downloaded from References This article cites 166 articles, 73 of which you can access for free at: http://www.jimmunol.org/content/198/6/2223.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 October 1, 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 © 2017 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Th eJournal of Brief Reviews Immunology The Importance of Dendritic Cells in Maintaining Immune Tolerance x { Cindy Audiger,*,†,1 M. Jubayer Rahman,‡,1 Tae Jin Yun, , Kristin V. Tarbell,‡ and Sylvie Lesage*,† Immune tolerance is necessary to prevent the immune specific depletion of CD11c+ cells (3).
    [Show full text]
  • Understanding the Immune System: How It Works
    Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute Understanding the Immune System How It Works U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH National Institute of Allergy and Infectious Diseases National Cancer Institute NIH Publication No. 03-5423 September 2003 www.niaid.nih.gov www.nci.nih.gov Contents 1 Introduction 2 Self and Nonself 3 The Structure of the Immune System 7 Immune Cells and Their Products 19 Mounting an Immune Response 24 Immunity: Natural and Acquired 28 Disorders of the Immune System 34 Immunology and Transplants 36 Immunity and Cancer 39 The Immune System and the Nervous System 40 Frontiers in Immunology 45 Summary 47 Glossary Introduction he immune system is a network of Tcells, tissues*, and organs that work together to defend the body against attacks by “foreign” invaders. These are primarily microbes (germs)—tiny, infection-causing Bacteria: organisms such as bacteria, viruses, streptococci parasites, and fungi. Because the human body provides an ideal environment for many microbes, they try to break in. It is the immune system’s job to keep them out or, failing that, to seek out and destroy them. Virus: When the immune system hits the wrong herpes virus target or is crippled, however, it can unleash a torrent of diseases, including allergy, arthritis, or AIDS. The immune system is amazingly complex. It can recognize and remember millions of Parasite: different enemies, and it can produce schistosome secretions and cells to match up with and wipe out each one of them.
    [Show full text]
  • Clonal Deletion of Autoreactive B Lymphocytes in Bone Marrow
    Proc. Nati. Acad. Sci. USA Vol. 86, pp. 8039-8043, October 1989 Immunology Clonal deletion of autoreactive B lymphocytes in bone marrow chimeras (immunological tolerance/transgenic mice/histocompatibility complex) DAVID NEMAZEE*t AND KURT BUERKIt *Basel Institute for Immunology, Postfach CH-4005, Basel, Switzerland; and tPrecinical Research, Sandoz, Ltd., CH-4002, Basel, Switzerland Communicated by Philippa Marrack, July 24, 1989 (receivedfor review June 17, 1989) ABSTRACT To study the fate of developing B cells in the mice that either did or did not bear the H-2k antigens to which presence and absence of the autoantigens to which they react, the transgenic antibody reacts (H-2Kk and H-2Dk). chimeric mice were constructed by ij'ecting bone marrow cells A potential difficulty with studying tolerance to H-2k in our from mice transgenic for rearranged immunoglobulin genes system with genetic crosses was that, because the B cells in encoding an anti-H-2Kk antibody into irradiated recipients that the tolerant animals also bore H-2 class I antigens, it was not did or did not express the H-2Kk antigen. In the presence of clear whether it was necessary for the H-2k antigens to be H-2Kk, the anti-H-2Kk-specific B cells were deleted from the coexpressed on the transgenic B cells themselves to achieve spleen and lymph nodes, whereas in its absence, anti-H-2Kk tolerance. In this report we describe the tolerance phenotype cells were abundant. B cells bearing a low level of membrane of irradiation bone marrow chimeras in which anti-H-2k immunoglobulin with the anti-H-2Kk idiotype were found in the transgenic B cells that lack the H-2k antigens develop in hosts bone marrows of H-2Kk recipients, suggesting that clonal that bear or do not bear H-2k antigens.
    [Show full text]
  • Induction of Peripheral Tolerance in Ongoing Autoimmune Inflammation Equirr Es Interleukin 27 Signaling in Dendritic Cells
    Thomas Jefferson University Jefferson Digital Commons Department of Neurology Faculty Papers Department of Neurology 10-27-2017 Induction of peripheral tolerance in ongoing autoimmune inflammation equirr es interleukin 27 signaling in dendritic cells Rodolfo Thome Thomas Jefferson University Jason N. Moore Thomas Jefferson University Elisabeth R. Mari Thomas Jefferson University Javad Rasouli Thomas Jefferson University Follow this and additional works at: https://jdc.jefferson.edu/neurologyfp Part of the Medical Immunology Commons, and the Neurology Commons Let us know how access to this document benefits ouy Recommended Citation Thome, Rodolfo; Moore, Jason N.; Mari, Elisabeth R.; and Rasouli, Javad, "Induction of peripheral tolerance in ongoing autoimmune inflammation equirr es interleukin 27 signaling in dendritic cells" (2017). Department of Neurology Faculty Papers. Paper 139. https://jdc.jefferson.edu/neurologyfp/139 This Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of Thomas Jefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarly publications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers and interested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion in Department of Neurology Faculty Papers by an authorized administrator of the Jefferson Digital Commons. For more information, please contact: [email protected]. ORIGINAL RESEARCH published: 27 October 2017 doi: 10.3389/fimmu.2017.01392 Induction of Peripheral Tolerance in Ongoing autoimmune inflammation Requires Interleukin 27 Signaling in Dendritic Cells Rodolfo Thomé1, Jason N.
    [Show full text]