Genetic Models of Immune and Inflammatory Diseases PDF
Preview Genetic Models of Immune and Inflammatory Diseases
Serono Symposia USA Norwell, Massachusetts Springer New York Berlin Heidelberg Barcelona Budapest Hong Kong London Milan Paris Santa Clara Singapore Tokyo PROCEEDINGS IN THE SERONO SYMPOSIA USA SERIES GENETIC MODELS OF IMMUNE AND INFLAMMATORY DISEASES Edited by Abul K. Abbas and Richard A. Flavell MOLECULAR AND CELLULAR ASPECTS OF PERIIMPLANTATION PROCESSES Edited by S.K. Dey THE SOMATOTROPHIC AXIS AND THE REPRODUCTIVE PROCESS IN HEALTH AND DISEASE Edited by Eli Y. Adashi and Michael O. Thorner GHRH, GH, AND IGF-I: Basic and Clinical Advances Edited by Marc R. Blackman, S. Mitchell Harman, Jesse Roth, and Jay R. Shapiro IMMUNOBIOLOGY OF REPRODUCTION Edited by Joan S. Hunt FUNCTION OF SOMATIC CELLS IN THE TESTIS Edited by Andrzej Bartke GLYCOPROTEIN HORMONES: Structure, Function, and Clinica/lmplications Edited by Joyce W. Lustbader, David Puett, and Raymond W. Ruddon GROWTH HORMONE II: Basic and Clinical Aspects Edited by Barry B. Bercu and Richard F. Walker TROPHOBLAST CELLS: Pathways for Maternal-Embryonic Commllnication Edited by Michael J. Soares. Stuart Handwerger, and Frank Talamantes IN VITRO FERTILIZA TION AND EMBRYO TRANSFER IN PRIMATES Edited by Don P. Wolf. Richard L. Stouffer, and Robert M. Brenner OVARIAN CELL INTERACTIONS: Genes to Physiology Edited by Aaron J.W. Hsueh and David W. Schomberg CELL BIOLOGY AND BIOTECHNOLOGY: Novel Approaches to Increased Cellular Productivity Edited by Melvin S. Oka and Randall G. Rupp PREIMPLANTA TION EMBRYO DEVELOPMENT Edited by Barry D. Bavister MOLECULAR BASIS OF REPRODUCTIVE ENDOCRINOLOGY Edited by Peter C.K. Leung. Aaron J.W. Hsueh. and Henry G. Friesen MODES OF ACTION OF GnRH AND GnRH ANALOGS Edited by William F. Crowley. Jr.. and P. Michael Conn Continlled after Index Serono Symposia USA Norwell, Massachusetts Abul K. Abbas Richard A. Flavell Editors Genetic Models of Immune and Inflammatory Diseases With 23 Figures i Springer Abul K. Abbas, M.D. Richard A. Flavell. Ph.D. Department of Pathology Section of Immunobiology Brigham and W omen'S Hospital Yale University School of Medicine Harvard Medical School New Haven, cr 06520 Boston. MA 02115 USA USA Proceedings of the International Symposium on Gene tic Models of Immune and Inftammatory Diseases sponsored by Strano Symposia USA. Inc .. hdd October 20 to 23. 1994. in Savannah. Georgia . For information on previous volumes. please contact Strono Symposia USA. Inc. Ubn.ry of Congre505 Cataloging.in .Publieltion Dati Gene tic models of immune and inflammatory diseases/edited by Aool K. Abb.s and Richard A. R lvell. p. Cm. ~ Proceedings of the International Symposium on Genetic Models of Im mune and Inflammatory Dis· el ses, sponsored by Serono Symposia USA. Inc .. held October 20 to 23. 1994. in Savannah. Georgian_T. p. \/erso. Includes biblioJ!:raphical references and indue$. ISBN.13,978-1-4612-7520-6 .·ISIIN·1J: 9711·1-4612·2376-4 001: 10.100719711-1..01612·2376-4 I. Autoimmunily-Animal mode ll-Congre·sKs. 2. Inflammation- Immunological aspects-Animal model!-CongrC$5C5. 3. Tn.rugenie miee-CongrCSKS.. 4. Cytokines-Plthophysiology- Animal models--Con&resses. I. Abbas. Abul K. II . Serono Symposia. USA. Ill . Inlernational Symposium on GeTlC'tit Models of Immu~ and Inflammatory DisclOSC$ (1994: $annn.h. Ga.) ]DNLM: I. Immunily-genetic:s--<ongresses. 2. AUloimmunity-geTlC'ti<:s--«Jngresses. 1. Cytokines- geTlC'lics--oongresses. 4. Immunologie Discascs-senetic:s-oongres5C$. 5. Models. Qc,netit--o:mgres5C$. OW 540 G328 I996J ORI88.3.G46 1996 616.07"9-dt2O 9546669 Prinled on acid·free paper. Cl I996 Springer· Verl ag Ne .. York. Inc. Softconr reprinl of the hardco\lcr I ~t edition 1996 All riJhts reserved. This work may nOi be translated or copied in ..h ole or in part ..i thout the ..r illen permission of the publisher (Springer·Vertag Ne .. York. In( .• 175 Fi flh Avenue. Ne .. York. NY ]0010. USA). except for brief uoerpU in connection ""ith re~icwsor scholar1y anal )"$'" Use in connection with any form of informalion storage and retrieval . electronic adaptation. compuler soft ....r e. or by limilar or dit.t;imil,. me thodology now known or hereafter developed is forbidden . The usc of general ~pti~ names. tn.de names. tn.demarb. etc .. in this publication. even if the former Ire nOI especially identified. is not to be laken.s a si,n that such namn . as undenlood by tM Tr;w;lt Marks I mI Merchandise Marks Act. may Iccordin,ly be used freely by anyone. While the advice and infonnation in this boo); are believed to be true and accurate at the date of going to pre505. neither the authors. nor the editon. nor the publishe r. nor Serono Symposia USA. Inc .. nor Serono Laboratories. Inc .• Can accept any legal responsibilily for any errors Or omissions Ihat may be made. The publisher makes no warranty. e~pre505 or implied. wilh respect co Ihe malerial contained herein. Permi$llion 10 photocopy for internal or pel"$Onal use. Or the intcrnal or peT$Onl luSt of specific clients, is ,ranted by Springer· Verlag Ne .. York. Inc .• fOf libraries registered with lhe Copyrighl Clearance Cenler (CCC). pro~ided that the base fee of SS.OO per copy. plus $0.20 pcr page is p.id directly to CCc. 222 Rose ..o od Ori~. Oanven. MA 01923. USA. Special requem should be Iddre$$ed directly LO Springcr- Verlag Ne .. York. Inc .• 175 Fifth Avenue. Ne .. York. NY 10010. USA. Produetion coordinated by Chernow Edi torial Sef\liccs. Inc.. and managed by Francine McNeill; manufac· Hlrin, supcf\lised by Jeffrey Taub. Typeset by 8Qt...ct Type5Cuer Ltd .. Hon, Kong. 987654321 I SJ)N· 13 : 978·1-4612.7S2~ Springer-Ve rlag Ne .. York Berlin Heidelberg SPIN 10524771 GENETIC MODELS OF IMMUNE AND INFLAMMATORY DISEASES Scientific Committee Abul K. Abbas, M.D. Harvard Medical School Boston, Massachusetts Richard A. Flavell, Ph.D. Yale University School of Medicine New Haven, Connecticut Organizing Secretary Leslie Nies Serono Symposia USA, Inc. 100 Longwater Circle Norwell, Massachusetts Preface This book contains the proceedings of the Serono Symposia USA interna- tional symposium on Genetic Models of Immune and Inflammatory Dis- eases held on October 20 to 23, 1994, in Savannah, Georgia. The advent of methods for introducing genes into the germlines of mice, and for targeted disruption of particular genes by homologous recombination, has provided scientists in many disciplines with an extraordinarily powerful set of analyti- cal tools. Some of the most informative applications of transgenic and gene knockout technology have been in studies of lymphocyte development and activation. The goal of this symposium was to bring together investigators using these genetic approaches for analyzing the immune system, with a view to defining common themes and novel directions. Transgenic mice have a wide variety of important applications in immu- nology. Defined proteins can be expressed in selected tissues throughout development, thus acquiring the essential characteristic of "self" antigens. Such models have been used to study how immune responses to these artificially created "self" antigens are controlled. Antigen receptors of lym- phocytes have been expressed as transgenes, and because lymphocytes are endowed with the unique property of allelic exclusion, such transgenic mice become essentially monospecific. Immunomodulatory agents have been expressed in defined tissues or throughout the body, providing tools for studying the functional consequences of dysregulated expression of biologi- cal response modifiers. The achievements that have come from analyses of gene knockout mice are perhaps even more remarkable. The obligatory roles of many proteins in lymphocyte development and function have been definitively established in knockouts. Equally impressive are the surprises that have resulted from many such studies, in which unexpected functions of particular proteins have been revealed. At the same time, many knockout mouse models have demonstrated the redundancy of cytokines and regulatory proteins, and the efficiency of "backup" systems. The next phase in the applications of transgenic and knockout mice is in creating models for human diseases. This symposium strongly highlighted the value of these approaches, and the enormous potential of methods of vii viii Preface in vivo genetic manipulation for understanding pathologic disorders, such as autoimmune and infectious diseases. There seems little doubt that this potential will continue to be realized in the next few years. We would like to acknowledge our gratitude to Serono Symposia USA, Inc., for organizing the conference, and particularly to Leslie Nies and her staff for their invaluable assistance with the meeting and the proceedings. Luk van Parijs, a graduate student at Harvard, accepted the challenge of summarizing the conference and editing the proceedings, and did both tasks with care and thoughtfulness. ABUL K. ABBAS RICHARD A. FLAVELL Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Contributors .............................................. Xlll Part I. Autoimmunity 1. Intensification of Diabetes in B7-1 Transgenic Mice ....... 3 CHARLES A. JANEWAY, JR., FLORENCE SUSAN WONG, SYLVIE GUERDER, EVA-PIA REICH, IRENE VISINTIN, AND RICHARD A. FLAVELL 2. A Transgenic Window on Self-Reactive T Lymphocytes. . . . 16 JACQUES F.A.P. MILLER, WILLIAM R. HEATH, AND JANETTE ALLISON 3. Induction and Breaking of Peripheral Tolerance .... . . . . . . 22 GUNTER J. HAMMERLING, JUDITH ALFERINK, IRIS FERBER, ANDREAS LIMMER, AND BERND ARNOLD 4. T-Cell Development and Tolerance in Virus-Specific Transgenic Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 PAMELA S. OHASHI 5. Inflammatory Disease in HLA-B27 Transgenic Rats. . . . . . . 44 JOEL D. TAUROG AND ROBERT E. HAMMER Part II. Autoimmunity, Infections 6. The Role of CD40 Ligand in Regulation of Immune Response ................................. 53 IQBAL S. GREWAL, JIANCHAO XU, AND RICHARD A. FLAVELL IX x Contents 7. Adventures in Antigen Presentation. . . . . . . . . . . . . . . . . . . . . 69 DAVID La 8. The Effect of MHC Encoding Transgenes on IDDM in NOD Mice........................................... 82 RUBY QUARTEY PAPAFIO, DON HEALEY, LORRAINE O'REILLY, PATRICIA HUTCHINGS, SUE DAY, AND ANNE COOKE 9. The Immunology of Leishmania Major Infection in Mice. . . 89 RICHARD M. LOCKs LEY Part ill. Cytokines, Co-Stimulators, Tumor Immunity 10. The Regulatory Functions of Co-Stimulators Revealed in Transgenic Mice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 MICHAEL P. SETHNA, LUK VAN PARIJS, ARLENE H. SHARPE, GORDON J. FREEMAN, AND ABUL K. ABBAS 11. B7-Deficient Mice Reveal an Alternative Functional CTLA-4 Counterreceptor . . . . . . . . . . . . . . . . . . . . 107 FRANK BORRIELLO, ELIZABETH A. TIVOL, GORDON J. FREEMAN, AND ARLENE H. SHARPE 12. Cytokine Transgenic Mice and Autoimmunity . . . . . . . . . . . . 121 MYUNGcSHlK LEE AND NORA SARVETNICK 13. Gaining Insights into the Ontogeny and Activation of T Cells Through the Use of Gene-Targeted Mutant Mice ......... 129 TAK W. MAK 14. B7-Mediated Co-Stimulation of T Cells: CTLA-4 Can Deliver Inhibitory Signals ..................................... 138 MATTHEW KRUMMEL AND JAMES P. ALLISON Part IV. Cytokine Deletions 15. Lymphoid Organogenesis and Inflammation Are Mediated by Lymphotoxin ..... '" .. . .. . . ... . .. .... 149 ALEXANDER KRATZ, DONNA M. BARTEN, ANTONIO CAMPos-NETO, AND NANCY H. RUDDLE Contents Xl 16. The Role of Interferon-a in the Development of Type I Diabetes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 XIAOJIAN HUANG, BRUCE HULTGREN, SHARON PITTs-MEEK, JIM HULLY, JIM MACLACHLAN, NOEL DYBDAL, AND TIMOTHY A. STEWART 17. Cytokine-Deficient Mouse Mutants.. ...... . .... . . . . . . . .. 167 WERNER MOLLER Author Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
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