MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VII Molecular Determinants of Microbial Immunity

ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY

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NATHAN BACK, State University of New York at Buffalo

IRUN R. COHEN, The Weizmann Institute of Science

DAVID KRITCHEVSKY, Wistar Institute

ABEL LAJTHA, N. S. Kline Institute for Psychiatric Research

RODOLFO PAOLETTI, University of Milan

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MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VII Molecular Determinants of Microbial Immunity

Edited by

Sudhir Gupta University of California, Irvine lrvine, California

Alan Sher National Institutes of Health Bethesda, Maryland

and

RafiAhmed Emory University Atlanta, Georgia

SPRINGER SCIENCE+BUSINESS MEDIA, LLC

Llbrary of Congrass Cataloglng-In-Publlcatlon Data

Mechantsms of lyaphocyte actlvatton and tm.une regulatton VII: molecular qetermtnants of mtcrobtal tmmuntty / edtted by Sudhtr Gupta. Alan Sher. and Raft Ahmed.

p. em. -- (Advanees tn expertmental medtetne and btology v. 452)

Ineludes btbltographteal referenees and index. ISBN 978-1-4615-5355-7 (eBook)

DOI 10.1007/978-1-4615-5355-7 1. Immune responsa--Regulatton--Congresses. 2. Natural t •• unlty­

-Congresses. 3. Baetertal dtseases--I.munologteal aspeets--Congressas. 1. Gupta. Sudhtr. II. Sher. Alan. III. Ahmed. Raft. IV. Sertes. ORI86.M42 1998 616.07'95--dc21 98-40455

CIP

Proceedings ofthe Seventh International Conference on Lyrnphocyte Activation and Immune Regulation, held February 6 - 8, 1998, at Newport Beach, California

ISBN 978-1-4613-7443-5

© 1998 Springer Science+Business Media New York Origina11y published by Plenum Press, New York in 1998 Softcover reprint of the hardcover 1 st edition 1998

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PREFACE

During the last decade, rapid progress has been made in the area of microbial immu­nity. New conceptual frameworks have emerged with regard to the processing and presen­tation of peptides and nonpeptide antigens from microbes, especially bacteria, to T cells in the context of classical MHC class I and nonconventional MHC I molecules. Experimen­tal models have been instrumental in defining some of these pathways for generating pro­tective immune responses against microbes, which form the basis for the design of new vaccines. New evidence has stressed the importance of innate immunity in microbial in­fections. The concept of dichotomy within T helper cells has revealed the role of these cell types in resistance and susceptibility to microbial-mediated pathology. These latest devel­opments in microbial immunity are discussed in this volume.

Natural killer cell development is known to be regulated by the presence of MHC class I antigens. Receptors for MHC class I molecules on NK cells have been discovered. Interaction of these receptors with their specific ligands leads to inhibition of cytotoxicity. Vinay Kumar and colleagues review NK cell differentiation and ontogeny, and functions of NK cells in experimental animals. Lewis Lanier discusses the role of a newly discov­ered molecule, DAP 12, in KIR and other receptor-mediated signal transduction in NK cells. Eric Long describes the regulation of immune response by inhibitory receptors. Re­cent studies of the role of epithelial yo T cells, in addition to specific immune regulation, in innate immune response are discussed by Wendy Havran and associates.

The role ofCD4+ Thl and Th2 cells in the susceptibility and resistance to microbes, especially to protozoan, has been reviewed. Keats Nelms and colleagues provide an ac­count of the molecular steps in signaling via IL-4 receptor and the biological significance of IL-4-IL-4R interactions. Richard Locksley et al. review the mechanisms, including the role of genetic factors, of the differentiation of naive T helper cells into cytokine effector cells. Thl responses confer resistance, whereas Th2 responses confer susceptibility to L. major. Jacques Louis and his colleagues discuss the effector functions of Thl cells and early events in the development of Th2 cells in murine model of L. major. Robert Coff­man and Amy Beebe review the genetic control of T cell responses to L. major infection, and Edward Pearce and colleagues present data on the induction and function of Th2 cells during S. mansoni infection.

The general paradigm is that intracellular bacteria elicit Th I response; however, Ste­fan Kaufmann et al. have provided data, in experimental model systems, to suggest that IL-4 (Th2 response) is produced as an early response to several intracellular bacteria, fol­lowed by prolonged Thl response. Both CD4+ and CD8+ T cell responses are elicited in

v

vi Preface

response to M tuberculosis. Barry Bloom and his colleagues provide new data for the role of cytotoxic T cells in resistance to M. tuberculosis. Alan Sher and colleagues emphasize the role of dendritic cells in the initiation of host resistance to T. gondii. Michael Bevan, Rafi Ahmed, Christine Biron, and their colleagues discuss immune responses to viral in­fections. They present data regarding the role and dynamics of CD8+ T cells in infection with LCMV, and review endogenous innate cytokines during early viral infection and the role these cytokines play in promoting cell-mediated immunity.

During the last four years, major advances have been made in understanding the im­munopathogenesis of HIV infection. Edward Berger reviews the discovery of chemokine receptors (co-receptors for HIV entry and tropism), expansion of co-receptor repertoire, and the molecular mechanisms underlying HIV fusion and tropism. Bruce Walker and as­sociates discuss various HIV-I-specific responses in relation to progressive and nonpro­gressive HIV infection. In addition to the well-recognized role of neutralizing antibodies and cytotoxic T cells, they provide convincing evidence for the role of p24-specific T helper cells in the control of HIV infection. The SIV monkey model has provided most valuable information regarding mucosal transmission of HI V infection. Marian Neutra, us­ing experimental model systems, shows local induction of specific IgG and secretory IgA response and demonstrates a role for M cells in pathogen entry. Norman Letvin and col­leagues elucidate the development ofSIV-specific CD8+ T cells during primary SIV infec­tion in monkeys.

Rapid understanding of the nature of determinants that dictate the immunogenicity and specificity of immune response has contributed to the area of vaccine development. Douglas Fearon discusses the role of non structural determinants of antigen in regulating B cell activation mediated by B cell co-receptors CDI9, CD21, and CD22. DNA vaccines, which differ from traditional vaccines, have been shown to elicit effective T cell and B cell responses and have been instrumental in evaluating mechanisms of induction of im­mune response. Margaret Liu and her colleagues review various types of DNA vaccines and the mechanisms for the generation of specific immune response. Louis Miller and as­sociates discuss the status of vaccines against Falciparum malaria, and John Robbins and colleagues provide evidence for and highlight the fact that not all virulence factors are protective antigens in immunity to pertussis.

This book should be of interest primarily to researchers in immunology, microbiol­ogy, and vaccine development. It should also be of interest to academic pediatricians and internists specializing in infectious diseases and immunology.

The editors extend thanks to Miss Nancy 1. Doman for her excellent secretarial as­sistance.

Sudhir Gupta Alan Sher RafiAhmed

CONTENTS

INNATE DEFENSE MECHANISMS

1. Development of Self-Recognition Systems in Natural Killer Cells .......... . P. V. Sivakumar, N. S. Williams, I. 1. Puzanov, 1. D. Schatzle, M. Bennett,

and V. Kumar

2. Activating and Inhibitory NK Cell Receptors Lewis L. Lanier

13

3. Regulation ofImmune Responses by Inhibitory Receptors. . . . . . . . . . . . . . . . . . 19 Eric O. Long

4. Innate Functions of Epithelial yo T Cells ................................ 29 Wendy L. Havran, Yaping Chen, and Richard Boismenu

EFFECTOR CHOICE

5. Interleukin-4 Receptor Signalling Mechanisms and Their Biological Significance 37 Keats Nelms, Hua Huang, John Ryan, Achsah Keegan, and William E. Paul

6. Development of CD4+ Effector T Cells and Susceptibility to Infectious Diseases 45 Richard M. Locksley, Deborah 1. Fowell, Kanade Shinkai, Adil E. Wakil,

Dee Lacy, and Mark Bix

7. Anti-Leishmania Effector Functions of CD4+Thl Cells and Early Events Instructing Th2 Cell Development and Susceptibility to Leishmania major in BALB/c Mice .............................................. 53

Jacques A. Louis, Fatima Conceir;ao-Silva, Hayo Himmelrich, Fabienne Tacchini-Cottier, and Pascal Launois

8. Genetic Control of the T Cell Response to Leishmania major Infection. . . . . . . . 61 Robert L. Coffman and Amy M. Beebe

9. The Initiation and Function ofTh2 Responses during Infection with Schistosoma mansoni .......................................... 67

Edward 1. Pearce, Anne La Flamme, Elizabeth Sabin, and Laura Rosa Brunet

vii

viii Contents

REGULATION OF HOST RESISTANCE TO INTRACELLULAR PATHOGENS

10. Interleukin-4 Production in Response to Infection with Intracellular Bacteria. . . 75 Helen Collins, Inge E. A. Flesch, Masashi Emoto, and Stefan H. E. Kaufmann

11. Cytotoxic T Lymphocytes in Resistance to Tuberculosis ................... 85 Richard 1. Mazzaccaro, Steffen Stenger, Kenneth L. Rock,

Steven A. Porcelli, Michael B. Brenner, Robert L. Modlin, and Barry R. Bloom

12. The Role of Dendritic Cells in the Initiation of Host Resistance to Toxoplasma gondii . . .... ...... .... .. ... . .. . ........... .... .. .... .. . .. . ... 103

Alan Sher, Sara Hieny, Hugues Charest, Tanya Scharton-Kersten, Carmen Collazo, Ronald N. Germain, and Caetano Reis e Sousa

13. Dynamics of the CD8+ T Cell Response during Acute LCMV Infection. . . . . . . 111 Eric Butz and Michael 1. Bevan

14. In Vivo Dynamics of Anti-Viral CD8 T Cell Responses to Different Epitopes: An Evaluation of Bystander Activation in Primary and Secondary Responses to Viral Infection .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

Kaja Murali-Krishna, John D. Altman, M. Suresh, David Sourdive, Allan Zajac, and Rafi Ahmed

15. Early Cytokine Responses to Viral Infections and Their Roles in Shaping Endogenous Cellular Immunity .................................. 143

Christine A. Biron, Leslie P. Cousens, Melanie C. Ruzek, Helen C. Su, and Thais P. Salazar-Mather

IMMUNOPATHOGENESIS OF HIV-l INFECTION

16. HIV Entry and Tropism: When One Receptor Is Not Enough. . . . . . . . . . . . . . . . 151 Edward A. Berger

17. Immune Control of HI V-I Replication. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 159 Bruce D. Walker, Eric S. Rosenberg, Christine M. Hay, Nes1i Basgoz, and

OttoO. Yang

18. HIV Transmission and Immune Protection at Mucosal Surfaces Marian R. Neutra

169

19. The CD8+ T Lymphocyte Response during Primary SIVmac Infection ........ 177 Norman L. Letvin, Yasuhiro Yasutomi, Ling Shen, Keith A. Reimann,

Zheng Wei Chen, Jom E. Schmitz, and Marcelo J. Kuroda

NEW APPROACHES TO VACCINE DEVELOPMENT

20. Non-Structural Determinants ofImmunogenicity and the B Cell Co-Receptors, CDl9, CD21, and CD22 ....... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181

Douglas T. Fearon

Contents ix

21. DNA Vaccines: Mechanisms for Generation of Immune Responses . . . . . . . . . . . 187 M. A. Liu, T.-M. Fu, J. J. Donnelly, M. J. Caulfield, and J. B. Ulmer

22. Vaccines against the Blood Stages of Falciparum Malaria .................. 193 Louis H. Miller, Michael F. Good, and David C. Kaslow

23. Immunity to Pertussis: Not All Virulence Factors Are Protective Antigens 207 John B. Robbins, Rachel Schneerson, Dolores A. Bryla, Birger Trollfors,

John Taranger, and Teresa Lagergdrd

Index. . .. .. .. . .. .. . . . .. . . . . . . . ... .. .... .. . .. . . . . . . . ..... ... . . . . . . . . . .. 219

MECHANISMS OF LYMPHOCYTE ACTIVATION AND IMMUNE REGULATION VII Molecular Determinants of Microbial Immunity