DOCSLIB.ORG

Rac-King up New Roles in Haematopoiesis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Rac-King up New Roles in Haematopoiesis HIGHLIGHTS numbers of pro-B, pre-B and imma- SIGNALLING IN BRIEF ture B cells in the bone marrow, but reduced numbers of B cells at later Rac-king up developmental stages in the spleen NATURAL KILLER CELLS and lymph nodes. In the absence of new roles in both Rac1 and Rac2, B-cell develop- The mature activating natural killer cell immunologic ment seems to be blocked at the synapse is formed in distinct stages. haematopoiesis transitional type 1 B-cell stage in the Orange, J. S. et al. Proc. Natl Acad. Sci. USA 100, 14151–14156 (2003) spleen. Rac1 and Rac2 guanosine triphos- Recent studies have shown activa- The interface between a natural killer (NK) cell and its target cell phatases (GTPases) are crucial sig- tion of Rac1 after B-cell receptor — the activating NK-cell immunological synapse — is highly nalling regulators in eukaryotic (BCR) stimulation, and signals from organized. In this study, Orange et al. show that CD2 and CD11b, cells, acting downstream of various the BCR are known to be crucial for similar to CD11a, co-localize with filamentous actin in the cellular receptors. Two studies pub- B-cell development, so are BCR sig- peripheral supramolecular activation cluster (pSMAC), whereas lished in Science have used condi- nalling defects responsible for the perforin accumulates in the central SMAC (cSMAC). Polarization tional gene targeting to clarify the observed phenotype of Rac1BRac2–/– of CD2, CD11a and CD11b to the pSMAC was dependent on roles of Rac1 and Rac2 in particular mice? Rac2–/– and Rac1–/+Rac2–/– actin polymerization and Wiskott-Aldrich syndrome protein aspects of haematopoietic-cell mature B cells stimulated with an (WASP), but independent of microtubule function. By contrast, differentiation. IgM-specific antibody had decreased perforin accumulation in the cSMAC was dependent on actin Gu et al. looked at the differential survival compared with wild-type polymerization, WASP and microtubule function. In addition, activity of Rac1 and Rac2 in B cells, which correlated with the rate of cSMAC perforin accumulation was slower than the haematopoietic stem/progenitor cells decreased induction of the anti- recruitment of receptors to the pSMAC, indicating that formation of the NK-cell immunological synapse is a highly regulated, (HSC/Ps). As Rac1 deficiency is apoptotic protein Bcl-XL.These embryonic lethal, they generated B cells also proliferated less than sequential process. conditional Rac1-knockout mice. wild-type cells. This was shown to be Deficiency of Rac1 inhibited the due to decreased induction of the MUCOSAL IMMUNOLOGY ability of HSC/Ps to reconstitute cell-cycle regulator cyclin D2 after haematopoiesis in an engraftment stimulation. So, Rac1 and Rac2 Spheniscins: avian β-defensins in preserved stomach model (which requires adhesion and transduce BCR signals for B-cell sur- contents of the king penguin, Aptenodytes proliferation in the bone marrow), vival and entry into the cell cycle. patagonicus. and the absence of both Rac1 and Finally, in contrast to wild-type cells, Thouzeau, C. et al. J. Biol. Chem. 2 October 2003 (doi:10.1074/jbc.M306839200) Rac2 led to the movement of progen- BAFF could not increase the survival In this paper, Thouzeau and colleagues have identified two new itor cells out of the bone marrow and of Rac1BRac2–/– immature B cells, avian antimicrobial peptides in the stomach of the male king into the peripheral circulation, as a and this was probably the result of penguin. These peptides, known as spheniscin 1 and 2, belong result of decreased adhesion to decreased expression of BAFF recep- to the β-defensin family and have broad antimicrobial activity fibronectin. Rac1 and Rac2 were also tor (BAFFR). Rac1 and Rac2 were against pathogenic bacteria and fungi. The levels of spheniscin shown to have roles in regulating the shown to transduce BCR signals lead- 1 and 2 are higher during periods of food storage than when cytoskeletal changes that are required ing to the upregulation of expression the birds are digesting, and interestingly, a drop in spheniscin for engraftment and mobilization. of BAFFR messenger RNA. levels correlated with a change from food storage to digestion. Rac1–/–, and to a greater extent These two studies show that in These antimicrobial peptides act to protect the surface of the Rac1–/–Rac2–/–, HSC/Ps had reduced both B cells and HSC/Ps, Rac1 and bird’s gastrointestinal tract from damage or invasion, and proliferation in response to growth Rac2 have essential roles in control- might be important for the long-term preservation of stored factors in vitro,correlating with ling proliferation and survival. food, which can be important for chick survival. decreased levels of cyclin D1 and Furthermore, despite their sequence phosphorylation of extracellular similarity, the two GTPases seem to signal-regulated kinase (ERK), and have partially non-redundant physi- increased levels of the cyclin- ological functions. Gu et al.con- dependent kinase inhibitor KIP1. By firmed this functional distinction in contrast, Rac2–/– cells were more sus- neutrophils, in which Rac2 seems to ceptible to apoptosis after growth- be the main GTPase regulating factor stimulation, associated with directed migration and superoxide reduced Akt activation. Therefore, it generation, whereas Rac1 regulates seems that Rac1 regulates entry into neutrophil shape. the cell cycle, whereas Rac2 mainly Kirsty Minton regulates cell survival. Walmsley et al.looked further References and links ORIGINAL RESEARCH PAPERS Gu, Y. et al. downstream at B-cell development Hematopoietic cell regulation by Rac1 and Rac2 by generating, for the first time, mice guanosine triphosphatases. Science 302, with a conditional deletion of Rac1 445–449 (2003) | Walmsley, M. J. et al. Critical B roles for Rac1 and Rac2 GTPases in B cell in the B-cell lineage (Rac1 mice). development and signaling. Science 302, Rac1BRac2–/– mice had normal 459–462 (2003) NATURE REVIEWS | IMMUNOLOGY VOLUME 3 | DECEMBER 2003 | 925 HIGHLIGHTS LYMPHOCYTE MIGRATION The ectodomain of the adhesion mol- evidence that naive T-cell trafficking is ecule L-selectin — which is crucial for not regulated by L-selectin shedding. T-cell migration from the bloodstream The authors further investigated Restricted entry into lymph nodes into peripheral lymph nodes (PLNs) the importance of L-selectin shedding — is proteolytically shed from the cell in T-cell rolling in vitro,using a hydro- surface after cross-linking. A new dynamic flow model, and in T-cell study by Galkina et al. has now defined trafficking in vivo after T-cell transfer that L-selectin shedding shapes the to normal or recombinase-activating migration pattern of T cells after anti- gene 1 (Rag1)-deficient mice. In vitro, gen activation, but that it is not the number of rolling L∆P and WT T required for naive T-cell trafficking. cells, as well as their rolling velocity L-selectin mediates tethering and and behaviour, was the same. In vivo, rolling of naive T cells in high transferred WT and L∆P naive T cells endothelial venules (HEVs) prior to migrated in equal numbers to the their migration to the PLNs. To inves- PLNs. Together, these studies indicate tigate the importance of L-selectin clearly that naive T-cell homing to the shedding in this process, Ann Ager PLNs is independent of L-selectin and colleagues generated endogenous shedding. L-selectin-deficient mice transgenic After activation, T cells downregu- for either wild-type L-selectin (WT) late the expression of L-selectin and or uncleavable L-selectin (L∆P) in T their migration patterns change. cells. The percentage of T cells in the Antigen-specific L-selectin downregu- PLNs of these animals was not statisti- lation was shown to be mediated by cally different, providing preliminary L-selectin shedding using offspring of T-CELL SIGNALLING Stimulation of human peripheral blood T cells with CD4-specific antibodies induced tyrosine phosphorylation of LIME by protein tyrosine kinases, including LCK. A new adaptor in the LIME-light Phosphorylation of distinct tyrosine residues mediated the association of LIME Several transmembrane adaptor proteins Several signalling molecules, including with LCK and the negative regulator of SRC found in lipid rafts have been shown to the p85 regulatory subunit of kinases, CSK kinase, indicating that LIME influence the outcome of immunoreceptor phosphatidylinositol 3-kinase (PI3K) and phosphorylation can direct LCK and CSK signalling in lymphocytes. Two studies in growth factor receptor-bound protein 2 recruitment to lipid rafts. The Journal of Experimental Medicine have (GRB2), were found to associate with LIME, LIME-associated LCK was phosphorylated now defined a new transmembrane adaptor and LIME-specific signals were shown to at both the negative and positive regulatory molecule — LIME (LCK-interacting induce the phosphorylation of JUN tyrosine residues, and overexpression of membrane molecule) — which is involved in N-terminal kinase (JNK) and extracellular LIME induced an enhanced calcium regulating LCK-transduced signals in T cells. signal-regulated kinase 1 (ERK1)/ERK2. response to TCR triggering by CD3-specific Using a tyrosine phosphorylation- Together, the results presented by Yun and antibodies. These observations led Horejˇ ˇsí dependent yeast two-hybrid system, Hur et al. colleagues indicate that through its association and colleagues to suggest that after TCR and identified LIME as a protein that associates with LCK, LIME has a role in several signalling CD4 co-ligation, LIME might potentiate
Load more

Recommended publications
  • Horse Gamma Globulin Stabilized in 0.3 Molar Glycine to a Ph of Approximately 6.8
    LPD Reference: ATG-SIN-0414/1 Date of Last Revision: 08 September 2014 Country: Singapore Reference document: CDS Version 3.0, effective date: 17-Mar-2014 Reason for change: LPD update in accordance with CDS 3.0 ; 2014-09-08 IR: 1. Remove entire proposed subsection <Renal Transplant Prophylaxis> under ‘Pharmacodynamic Properties - Clinical Studies’ & 2. Relocate paragraph “Clinical trials […] standard supportive care alone” from <Therapeutic Indications> to < Pharmacodynamic Properties - Clinical Studies>, subsection <Aplastic Anemia>. Atgam® lymphocyte immune globulin, anti-thymocyte globulin [equine] sterile solution For Intravenous Use only DESCRIPTION ATGAM Sterile Solution contains lymphocyte immune globulin, anti-thymocyte globulin [equine]. It is the purified, concentrated, and sterile gamma globulin, primarily monomeric IgG, from hyperimmune serum of horses immunized with human thymus lymphocytes. Anti-thymocyte globulin (equine) is a transparent to slightly opalescent aqueous protein solution. It may appear colorless to faintly pink or brown and is nearly odorless. It may develop a slight granular or flaky deposit during storage. (For information about in-line filters, see Infusion Instructions in the POSOLOGY AND METHOD OF ADMINISTRATION.) Before release for clinical use, each lot of anti-thymocyte globulin (equine) is tested to assure its ability to inhibit rosette formation between human peripheral lymphocytes and sheep red blood cells in vitro. In each lot, antibody activity against human red blood cells and platelets is also measured and determined to be within acceptable limits. Only lots that test negative for antihuman serum protein antibody, antiglomerular basement membrane antibody and pyrogens are released. Each milliliter of anti-thymocyte globulin (equine) contains 50 mg of horse gamma globulin stabilized in 0.3 molar glycine to a pH of approximately 6.8.
    [Show full text]
  • 1-Phosphate-Lyase-Deficient Mice Development in Sphingosine
    Discontinued Postnatal Thymocyte Development in Sphingosine 1-Phosphate-Lyase-Deficient Mice This information is current as Claudia Weber, Andreas Krueger, Anika Münk, Constantin of October 1, 2021. Bode, Paul P. Van Veldhoven and Markus H. Gräler J Immunol 2009; 183:4292-4301; Prepublished online 11 September 2009; doi: 10.4049/jimmunol.0901724 http://www.jimmunol.org/content/183/7/4292 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2009/09/10/jimmunol.090172 Material 4.DC1 http://www.jimmunol.org/ References This article cites 48 articles, 20 of which you can access for free at: http://www.jimmunol.org/content/183/7/4292.full#ref-list-1 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 October 1, 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 © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Discontinued Postnatal Thymocyte Development in Sphingosine 1-Phosphate-Lyase-Deficient Mice1,2 Claudia Weber,3* Andreas Krueger,3* Anika Mu¨nk,* Constantin Bode,* Paul P.
    [Show full text]
  • 3156.Full.Pdf
    A New IFN-Like Cytokine, Limitin Modulates the Immune Response Without Influencing Thymocyte Development This information is current as Isao Takahashi, Hiroshi Kosaka, Kenji Oritani, William R. of October 1, 2021. Heath, Jun Ishikawa, Yu Okajima, Megumu Ogawa, Sin-ichiro Kawamoto, Masahide Yamada, Hiroaki Azukizawa, Satoshi Itami, Kunihiko Yoshikawa, Yoshiaki Tomiyama and Yuji Matsuzawa J Immunol 2001; 167:3156-3163; ; doi: 10.4049/jimmunol.167.6.3156 Downloaded from http://www.jimmunol.org/content/167/6/3156 References This article cites 68 articles, 28 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/167/6/3156.full#ref-list-1 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 October 1, 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 © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. A New IFN-Like Cytokine, Limitin Modulates the Immune Response Without Influencing Thymocyte Development1 Isao Takahashi,* Hiroshi Kosaka,† Kenji Oritani,2* William R.
    [Show full text]
  • Immunology: Improving on Nature Review in the Twenty-First Century
    CORE Metadata, citation and similar papers at core.ac.uk Provided by Elsevier - Publisher Connector Cell, Vol. 100, 129±138, January 7, 2000, Copyright 2000 by Cell Press Immunology: Improving on Nature Review in the Twenty-First Century Abul K. Abbas* and Charles A. Janeway Jr.² notion at the time, one that challenged existing concepts *Department of Pathology of how proteins conformed to the shapes of other inter- University of California San Francisco School acting proteins. Nevertheless, the clonal selection the- of Medicine ory became the foundation for our understanding of the San Francisco, California 94123 specificity and development of immune responses. The ² Section of Immunobiology molecular understanding of how the diverse repertoire Yale University School of Medicine of antigen receptors is generated came with the studies New Haven, Connecticut 06520 of Susumu Tonegawa in the 1970s (Tonegawa et al., 1977). Based on this work, and its many subsequent refinements, it is now known that the antigen receptors Introduction of B and T lymphocytes are encoded by genes that are Immunology is the study of the body's defenses against produced by somatic recombination of gene segments infection. The birth of immunology as an experimental during maturation of the cells. The recombination pro- science dates to Edward Jenner's successful vaccina- cess is initiated by the RAG proteins, and presence of tion against smallpox in 1796 (Jenner, 1798). The world- RAG genes during phylogeny identifies the evolutionary wide acceptance of vaccination led to mankind's great- time of appearance of the adaptive immune system, est achievements in preventing disease, and smallpox which is just past the appearance of vertebrates (Agra- is the first and only human disease that has been eradi- wal et al., 1998; Hiom et al., 1998).
    [Show full text]
  • Molecular Regulation of Peripheral B Cells and Their Progeny in Immunity
    Downloaded from genesdev.cshlp.org on September 26, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW Molecular regulation of peripheral B cells and their progeny in immunity Mark R. Boothby,1,2 Emily Hodges,3 and James W. Thomas1,2 1Department of Pathology–Microbiology–Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA; 2Department of Medicine, Rheumatology Division, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA; 3Department of Biochemistry, Vanderbilt Genetics Institute, Nashville, Tennessee 37232, USA Mature B lymphocytes are crucial components of adap- potentials. A vast trove of findings illuminates the tran- tive immunity, a system essential for the evolutionary fit- scriptional regulation and chromatin modifications (for ness of mammals. Adaptive lymphocyte function requires convenience, referred to here as epigenetic) that program an initially naïve cell to proliferate extensively and its developmental progression from common lymphoid pro- progeny to have the capacity to assume a variety of fates. genitors (CLPs) to the establishment of the naïve popu- These include either terminal differentiation (the long- lations of mature T and B cells (e.g., for review, see lived plasma cell) or metastable transcriptional repro- Busslinger 2004; Champhekar et al. 2015). Similarly, the gramming (germinal center and memory B cells). In this process of diversifying subsets of T cells after their activa- review, we focus principally on the regulation of differen- tion has been studied and reviewed intensively (Glimcher tiation and functional diversification of the “B2” subset. and Murphy 2000; Fang and Zhu 2017; Henning et al. An overview is combined with an account of more recent 2018). Mature B lymphocytes also have the potential to advances, including initial work on mechanisms that distribute their progeny among several distinct fates or eliminate DNA methylation and potential links between intermediate states after they have encountered a ligand intracellular metabolites and chromatin editing.
    [Show full text]
  • Cell-Independent Plasma Cell Production Involvement of Twisted
    Involvement of Twisted Gastrulation in T Cell-Independent Plasma Cell Production Sotiris Tsalavos, Katerina Segklia, Ourania Passa, Anna Petryk, Michael B. O'Connor and Daniel Graf This information is current as of September 26, 2021. J Immunol 2011; 186:6860-6870; Prepublished online 13 May 2011; doi: 10.4049/jimmunol.1001833 http://www.jimmunol.org/content/186/12/6860 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2011/05/13/jimmunol.100183 Material 3.DC1 References This article cites 53 articles, 20 of which you can access for free at: http://www.jimmunol.org/ http://www.jimmunol.org/content/186/12/6860.full#ref-list-1 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 26, 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 © 2011 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Involvement of Twisted Gastrulation in T Cell-Independent Plasma Cell Production Sotiris Tsalavos,* Katerina Segklia,* Ourania Passa,* Anna Petryk,†,‡ Michael B.
    [Show full text]
  • Equine Anti-Thymocyte Globulin (ATGAM) Administration in Patient
    Open Access Journal of Clinical Nephrology Case Report Equine Anti-Thymocyte Globulin (ATGAM) administration in patient ISSN 2576-9529 with previous rabbit Anti-Thymocyte Globulin (Thymoglobulin) induced serum sickness: A case report 1 2 3 *Address for Correspondence: Joseph B Pryor, Joseph B Pryor *, Ali J Olyaei , Joseph B Lockridge and Douglas J MD Candidate, Oregon Health and Science 4 Norman University, School of Medicine, Portland, Email: 1 [email protected] MD Candidate, Oregon Health and Science University, School of Medicine, Portland 2Professor of Medicine & Pharmacotherapy, Pharmacy Practice/ Nephrology & Hypertension, Submitted: 08 March 2018 Oregon State University/Oregon Health & Science University, Portland Approved: 22 March 2018 3 Published: 23 March 2018 Assistant Professor of Medicine & Medical Director, Division of Nephrology, Department of Medicine, Oregon Health and Science University and Portland VA Medical Center, Portland Copyright: 2018 Pryor JB. et al. This is 4Professor of Medicine & Director, Immunogenetics Laboratory, Division of Nephrology, Department an open access article distributed under the Creative Commons Attribution License, which of Medicine, Oregon Health and Science University and Portland VA Medical Center, Portland permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Keywords: Thymoglobulin; ATGAM; Serum sickness; Kidney transplantation Thymoglobulin is a rabbit-derived anti-thymocyte antibody directed at T-cells and commonly used for induction immunosuppression therapy in solid organ transplantation, especially in immunologically high risk kidney transplant recipients. Despite its frequent use and effi cacy, the heterologous makeup of thymoglobulin can induce the immune system resulting in serum sickness which typically presents with rash, fever, fatigue, and poly-arthralgia in the weeks following drug exposure.
    [Show full text]
  • Package Insert
    HIGHLIGHTS OF PRESCRIBING INFORMATION ---------------------DOSAGE FORMS AND STRENGTHS---------------------- These highlights do not include all the information needed to use • Single-use 10 mL vial containing 25 mg of anti-thymocyte globulin (rabbit) THYMOGLOBULIN® safely and effectively. See full prescribing lyophilized, sterile powder. (3) information for THYMOGLOBULIN. ------------------------------CONTRAINDICATIONS------------------------------- THYMOGLOBULIN (anti-thymocyte globulin [rabbit]) for intravenous Allergy or anaphylactic reaction to rabbit proteins or to any product use excipients, or active acute or chronic infections which contraindicate any Initial U.S. Approval: 1998 additional immunosuppression (4) WARNING: IMMUNOSUPPRESSION ----------------------WARNINGS AND PRECAUTIONS------------------------- ® • THYMOGLOBULIN should only be used by physicians experienced in THYMOGLOBULIN should only be used by physicians experienced in immunosuppressant therapy in transplantation. (5.1) immunosuppressive therapy in transplantation. (5.1) • Immune-mediated reactions: THYMOGLOBULIN infusion could result in ---------------------------RECENT MAJOR CHANGES--------------------------- an anaphylactic reaction. (5.2) Indications and Usage (1) 04/2017 • Infusion-associated reactions: Close compliance with the recommended Dosage and Administration (2.1, 2.2, 2.3, 2.4) 04/2017 infusion time may reduce the incidence and severity of infusion-associated Contraindications (4) 04/2017 reactions. (5.3) Warnings and Precautions (5.1, 5.2, 5.3, 5.5,
    [Show full text]
  • Cytokine Expression on Thymocyte Apoptosis and Th1/Th2 Synergistic
    Synergistic Effect of IL-2, IL-12, and IL-18 on Thymocyte Apoptosis and Th1/Th2 Cytokine Expression This information is current as Maria Cecilia Rodriguez-Galán, Jay H. Bream, Andrew Farr of September 23, 2021. and Howard A. Young J Immunol 2005; 174:2796-2804; ; doi: 10.4049/jimmunol.174.5.2796 http://www.jimmunol.org/content/174/5/2796 Downloaded from References This article cites 48 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/174/5/2796.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 23, 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 © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Synergistic Effect of IL-2, IL-12, and IL-18 on Thymocyte Apoptosis and Th1/Th2 Cytokine Expression1,2 Maria Cecilia Rodriguez-Gala´n,* Jay H. Bream,† Andrew Farr,‡ and Howard A.
    [Show full text]
  • The Thymus Is Relevant in the Migration of Mature Lymphocytes
    Cell and Tissue Research (2019) 376:19–24 https://doi.org/10.1007/s00441-019-02994-z MINI REVIEW The thymus is relevant in the migration of mature lymphocytes Reinhard Pabst1 Received: 11 September 2018 /Accepted: 15 January 2019 /Published online: 14 February 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract The thymus is a primary lymphoid organ where T lymphocyte proliferation and selection takes place. The different subsets of lymphocytes leave the thymus as recent thymic emigrants. Peripheral dendritic cells migrate to the thymus. In addition to the homing of hematopoietic progenitor cells to the thymus, there is evidence for lymphocyte entry from peripheral lymphoid tissues mainly into the medulla. The entry sites are the venules in the medullary part near to the cortex with a higher endothelium. Furthermore, there are also B lymphocytes in the thymus. The thymus is not only a primary lymphoid organ but is well integrated in lymphocyte traffic as shown in several different species. Keywords Thymus . Medulla . Lymphocyte entry . Peripheral lymphoid organs . Blymphocytes Introduction Zúñiga-Pflücker 2007). Rodewald (2007) included a cer- vical thymus in the mouse, which produces T cells only The thymus is normally taken as a typical primary lymphoid after birth. organ thus independent of the influx of mature lymphocytes Stem cells from the bone marrow enter this epithelial from the periphery (see textbooks of immunology, e.g., structure and differentiate into different subsets and Cowan et al. 2016,orofanatomy,seeStandring2016). form the structural backbone. There is a multistep cas- However, there are many data documenting the entry of lym- cade of adhesion molecules essential for bone marrow– phocytes from the blood and secondary lymphoid organs into derived progenitor cells to home to the thymus the thymus, which have mostly been neglected so far.
    [Show full text]
  • Thymocyte Development: Cytokines Have the Casting Vote
    RESEARCH HIGHLIGHTS Nature Reviews Immunology | AOP, published online 19 February 2010; doi:10.1038/nri2732 THYMOCYTE DEVELOPMENT Cytokines have the casting vote Signals through the T cell receptor other STAT molecules. The authors the TCR-associated tyrosine kinase (TCR) are crucial for the positive conclude that STAT-mediated ZAP70 were crossed with Socs1- selection of double-positive (DP) cytokine signalling is required for the knockout mice transgenic for the IL-7 thymocytes and for the differen- generation of most, if not all, CD8+ receptor α-chain to produce mice in tiation of CD4+ T cells. Far less thymocytes, which was supported by which thymocytes were arrested at a is known about how CD8+ T cell the total lack of CD8+ thymocytes in pre-selection DP stage, owing to a lack lineage specification occurs; this mice transgenic for the STAT signal- of TCR signalling, but were responsive study indicates that although TCR ling inhibitor suppressor of cytokine to IL-7. In vitro culture of purified DP signalling sets the stage for the differ- signalling 1 (SOCS1). thymocytes from these mice with IL-7 entiation of CD8+ T cells, signalling In an in vitro model of positive or transgenic intrathymic expression by cytokines such as interleukin-7 selection, the Runt-family transcrip- of IL-7 in vivo resulted in RUNX3 (IL-7) is the deciding factor. tion factor RUNX3 — which speci- expression by thymocytes and the dif- TCR-mediated positive selection fies the CD8+ T cell lineage — was ferentiation of CD8+ T cells expressing converts cytokine-unresponsive DP expressed only after stimulation markers of functional competence.
    [Show full text]
  • Davina Dadley-Moore
    RESEARCH HIGHLIGHTS of monoclonal antibodies specific early phase response when trans- for type II collagen together with ferred to mice that are deficient in lipopolysaccharide and is character- both T-bet and RAG2. Consistent IN BRIEF ized by an early innate phase followed with this role for DCs in the early by a later adaptive phase. Compared inflammatory phase, the authors with wild-type mice, the onset of showed that T-bet-deficient DCs pro- T-CELL DEVELOPMENT CAIA in T-bet-deficient mice was duced less of the pro-inflammatory Premature expression of chemokine receptor CCR9 delayed and was less severe in both mediators interleukin-1α and impairs T cell development. the initial and the late phases. CC-chemokine ligand 3 (CCL3) Uehara, S. et al. J. Immunol. 176, 75–84 (2006) Mice that are deficient in RAG2 and more CCL17, a ligand for the Only late CD4–CD8– double-negative (DN) thymocytes and + + (recombination-activating gene 2), TH2-cell-specific chemokine CD4 CD8 double-positive thymocytes express CC-chemokine which completely lack B and T cells, receptor CCR4, than wild-type DCs. receptor 9 (CCR9). To investigate whether expression of CCR9 developed early joint inflammation, Moreover, the ability of DCs to prime controls the migration of thymocytes and their retention in the but the later phase was attenuated. naive T cells in vivo was impaired thymus, Uehara et al. generated transgenic mice in which CCR9 + + And mice that are deficient in both in the absence of T-bet. was expressed throughout T-cell development. CD4 and CD8 single-positive (SP) thymocytes could exit the thymus, indicating T-bet and RAG2 were resistant to the In light of these results, that CCR9 downregulation is not essential for SP thymocyte induction of arthritis.
    [Show full text]