DOCSLIB.ORG

Thymocyte Binding to Human Thymic Epithelial Cells Is

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Thymocyte Binding to Human Thymic Epithelial Cells Is 0022-1 767/87/1382-0358SOZ.OO/O THEJOURNAL OF IMMUNOL~~Y Vol. 138.358-363.No. 2. January 15. 1987 Copyright 0 1987 by The American Association of Immunologists Printed in U.S.A. THYMOCYTEBINDING TO HUMAN THYMIC EPITHELIAL CELLS IS INHIBITED BY MONOCLONAL ANTIBODIESTO CD-2 AND LFA-3 ANTIGENS LEANNE WOLF VOLLGER," DEBBI T. TUCK,' TIMOTHY A. SPRINGER,* BARTON F. HAYNES,"' AND KAY H. SINGER"' From the *Departmentof Microbiology and Immunology, Divisionof Immunology and the 'Departmentof Medicine, Division of Rheumatology and Immunology, Duke UniversitySchool of Medicine. Durham,NC 27710;and the 'Laboratoryof Membrane IrnmunochemistrQ, Dana-Farber Cancer Institute. Boston,MA 021 15 With the use of cultured human thymic epithelial ing assay (7). In that study, TE-thymocyte binding was (TE) cells, we have previously shown that thymo- not blockedby antibodies to major histocompatibility cytes bind to TE cells in suspension in a rosette- complex (MHC) class I and class I1 antigens (7).To addi- forming assay. To identify cell surface molecules tionally define molecules involved in human TE-thymo- involved in human TE-thymocyterosette formation, cyte binding in vitro, we have investigated the ability of we assayed alarge panel of monoclonal antibodies monoclonal antibodies againsta wide variety of epithelial for their ability to inhibit rosette formation. We and lymphocyte antigens to inhibit TE-thymocyte bind- found anti-CD-2 (LFA-2, Tll), and anti-LFA-3 anti- ing. In this report, we identify two molecules, the CD-2 bodies all inhibited binding of TE cells to thymo- molecule (LFA-2, T1 1 , E-rosette receptor) on thymocytes, cytes. By using indirect immunofluorescence as- and the LFA-3 molecule on TE cells, which appear to be says, we determinedthat culturedTE cells were 90% LFA-3 positive and CD-2 negative, whereas thymo- involved in human TE-thymocyte binding invitro. cytes were 10%LFA-3 positive and 98% CD-2 posi- tive. Pretreatment of TE cells with anti-LFA-3 but MATERIALS AND METHODS not anti-LFA-2 inhibited TE-thymocyte binding.In Monoclonal antibodies. Antibodies against thelymphocyte func- contrast, pretreatment of thymocytes with anti-CD- tion associated antigen-1 (LFA-1) CY and p subunits, (TS1/22 and TS1/18, respectively), LFA-2 (TS2/18, TS1/8), and LFA-3 (TS2/9) 2 but not anti-LFA-3 antibodies inhibited TE-thy- antigens were raised against HLA-DR specific human cytotoxic T mocyte binding. ThusTE cell-thymocyte binding is lymphocyte clones (8)and were used as ascites or purified antibody. blocked by antibodiesto the CD-2 (T11) antigen on Antibody LM-2 was raised against granulocytes and detects theMac- thymocytes and by an antibodyto the LFA-3 antigen 1 CY subunit (Miller and Springer, manuscript in preparation). Anti- on TE cells. Because the CD-2 antigen has been bodies against human TE cells (TE-3, TE-4. TE-8, TE-15, TE-16, and TE-19) were raised against human thymic stroma and define implicated in T cell activation, these data suggest discrete stagesof TE cell maturation (9-1 1). Antibody 8AD6 against that a natural ligand for T cell activation via the early T cell precursors was generatedin our laboratory by using the CD-2 molecule is present on human thymic epithe- DU.528 human stem cell line (12)as immunizing antigen and lym- lial cells. phocyte hybrid techniques as described (10). Other anti-T cell anti- bodies were obtained through the Second International Workshop on Leukocyte Differentiation Antigens (13). Antibody 3F10 reacts with non-polymorphic MHC class I determinants (1 Antibody4). L243 Although the thymus is necessary for generation of reacts with non-polymorphic MHC class I1 determinants (15) and functionally mature T lymphocytes, the specific roles was obtained from the American Type Culture Collection (ATCC; that thymic microenvironment components play in pro- Rockville, MD). Anti-IgG-Fc receptor antibody (KFc79) was the gift motion of normal T cell maturation are not understood of Dr. T. Mohanakumar,Medical College of Virginia, Richmond, VA; anti-thymulin antibodies E8ClO and 1H6H10 (16. 17) were the gift (1-4). We have previously developed an in vitro system of Dr. M. Dardenne. Paris. Anti-keratin monoclonal antibody AE1 for the long-term growth of human thymic epithelial(TE)3 (18) was provided by Dr. T.-T. Sun, New York University School of cells (5).Moreover, we have shown TE cells can activate Medicine, New York. In vitro culture of human thymic epithelial cells. Thymus tissue autologous thymocytes in vitro, and serve as accessory was obtained at the time of corrective cardiovascular surgery from cells for phytohemagglutinin (PHA)-induced thymocyte 15 patients aged 7 mo to 16yr. Human TEcell cultures were initiated activation (6). by an explant technique,were propagated in enriched medium, and were subcultured as described (5). The A431 cell line (19) was Recently, we have described binding of both cortical obtained from Dr. J. DeLarco. National Institutes of Health, and was and medullary thymocytes to autologous and allogeneic passaged in Dulbecco's modified Eagle's medium (Grand IslandBio- cultured TE cells by using a TE-thymocyte rosette-form- logical Co.. Grand Island, NY) supplemented with 10% fetal calf serum (GIBCO), 100 pdml streptomycin, 100 IU/ml penicillin, and 0.25 &/ml amphotericin B (GIBCO). Received for publication September 16, 1986. Thymocytes. Thymocytes were gentlyteased from thymus tissue Accepted for publication September 29. 1986. and were purified by centrifugation through Ficoll-Hypaque (20). The costs of publication of this article were defrayed in part by the Cells were frozen slowly in RPMI 1640 (GIBCO) containing 20% fetal payment of page charges. Thts article must therefore be hereby marked calf serum (FCS), 7.5% dimethylsulfoxide (Sigma Chemical Co.. St.. advertisement in accordance wtth 18 U.S.C. Section 1734 solely to indi- Louis, MO). and 10 pg/ml gentamicin (Schering, Kenilworth. NJ). cate thisfact. This work was supported in part by Grants CA28936. K0400695, and were stored in liquid nitrogen. To thaw, thymocytes were incu- AM34808. and 5T32CA09058 from the National Institutes of Health. bated at 37°C for 1 hr in RPMI 1640 containing30% fetal calf serum, KHS is a Scholar of the Leukemia Societyof America. 100 pglml deoxyribonuclease I (Sigma), and 10p@ml gentamicin. Reprint requests to: Leanne Wolf Vollger. Duke University Medical Immunofluorescence. Indirectimmunofluorescence was per- Center, P.O.Box 2987, Durham, NC 27710. formed on cells in suspension, on frozen tissue sections, and on Abbreviations used in this paper: LFA, lymphocyte functton-associ- cytocentrifuge preparations as described in detail (21). P3X63/Ag8 ated antigen: TE, thymic epithelial. ascites fluid was used as a negative control in all assays. 358 HUMAN THYMOCYTES BIND THYMIC EPITHELIAL CELLS VIA CD-2 359 TABLE I In reciprocal washing experiments, 1 X 10' TE cells, 2 X lo6 A431 Monoclonal antlbodies that inhibit TE-thymocyte binding cells, or 40 X lo6 thymocyteswere preincubated with a 1/100 dilution of antibody in 400 plof RPMI-FCS for 30 min at 4'C. Percent In- Remaining free antibody was removed by washing cells twice (250 Antlbody Speclflclty hlbltlon f x G. 5 min. 4°C) in 15 ml of RPMI-FCS. Cells were then examined SEM for TE-thymocytebinding as described. Assays for inhibition of TE- TS2/9 LFA-3 912 5 thymocyte binding with antibody 3F10 (anti-MHC class I) and with TS 1/8 CD-2, LFA-2 91f 4 antibody L243 (anti-MHC class 11) were performed both in the pres- TS2/ 18 CD-2, LFA-2 91.C 1 ence of excess (unbound) antibody and after washing out excess 35.1 CD-2 96.C 0 antibody. T11/3Pt2H9 CD-2 93.C 3 T 1 1/ROLD2- 1H8 CD-2 93+ 3 TI 1/7T4-7A9 CD-2 83+ 7 RESULTS T56 CD-2 44 f 10 D66 CD-2 59 2 14 Screen of a panel of monoclonal antibodiesfor ability T 2/3Pt1 12B8 CD-6 15* 5 to inhibit TE-thymocyte binding. A large panel of anti- 12.1.5 CD-6 12* 3 lymphocyte and anti-epithelial monoclonal antibodies "Thymocytes were pretreated with monoclonal antibody as described in Materials and Methods. and TE or A431 cells were added. The data was tested for ability to inhibit binding of thymocytes to are expressed as mean percent inhibition of epithelial cell-thymocyte cultured TE or A431 cells. Of the antibodies tested,only binding. The datarepresent mean f SEM of three experiments. those directed against the CD-2 (LFA-2, T1 1, E-rosette TABLE I1 receptor) molecule and theLFA-3 molecule inhibited TE- Monoclonal antibodies that did not inhlblt TE-thqmocqte bindin.@ thymocyte and A43 1-thymocyte rosette formation(Table Antlbodv SDeClflCitV I). Anti-LFA-2 antibodies TS1/8 and TS2/18, as well as other anti-CD-2 antibodiesT11/3Pt2H9, T1 lROLD2- 3F10 Anti-HLA class I L243 Anti-HLA class I1 (la) 1H8, T11/7T47A9, and 35.1 blocked greater than 80% NA 1 /34 CD- 1 of TE-thymocyte or A431-thymocyte binding. The anti- T3 CD-3 T4 CD-4 CD2 antibodies D66 and T56 partially blocked TE-thy- 6-2 CD-5 mocyte binding (59and 44%inhibition, respectively) (Ta- 2H4 CD-5 2H4 ble I). D66 and T56have been shown to bind a subset of 3A1 CD-7 T8 CD-8 CD-2 positive peripheral blood T cells and to bind to a F1089-4-7 T200 distinct epitope on the CD-2 molecule (13, 22).We have 8AD6 Pan-thymocyte also observed that themonoclonal antibody TQl, which TSl/22 LFA- 1 TS1/18 LFA- 1 inhibitsE-rosette formation (22) andwas found by TE-3 Cortical thymic epithelium Knowles to bind to the CD-2 molecule (23), completely TE-4 Thymic subcapsular cortex and medulla inhibited thymocyte-A431 binding (not shown).
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]
  • 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.
    [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]