Interleukin 2

Interleukin 2 focuses on interleukin 2 (IL-2) and its impact on immunology. Topics covered include IL-2's mechanism of action, the structure of the IL-2 receptor, the characteristics of natural and recombinant human IL-2, regulation of IL-2 production by the T cell antigen receptor, how IL-2 binding induces the transcription of a novel set of genes, and the pathological roles of IL-2 receptor inducers in adult T cell leukemia. This book is comprised of 12 chapters and begins with a historical overview of IL-2, from the discovery of soluble mitogenic factors in culture media of stimulated lymphocytes to the discovery of IL-2 as the molecule responsible for stimulating T cell proliferation. The physicochemical and biological properties of purified recombinant IL-2 are then described, paying particular attention to natural IL-2 derived from human peripheral blood leukocytes. The chapters that follow discuss the different techniques used to gain insight into the functionally important regions of IL-2, the role of the T cell antigen receptor in regulating the production of IL-2, and the structure of the human high-affinity IL-2 receptor. The book also describes transmembrane signaling by IL-2, IL-2-inducible gene expression in T lymphocytes, abnormal IL-2 receptor expression in adult T cell leukemia, the use of IL-2 receptors in immunosuppressive therapy, and the use of IL-2 as a pharmacologic reagent. This book will be of interest to students and researchers in immunology and biochemistry.

Contributors

Preface

Foreword

1. Interleukin 2: A 10-Year Perspective

I. Introduction

II. Interleukin 2

III. The IL-2 Receptor

IV. IL-2 Receptor Structure

V. Functional Consequences of the IL-2 Receptor Bimolecular Structure

VI. α Chains Are Responsible for Stimulating Cell Cycle Progression

VII. The Regulation of IL-2 Receptor Expression

VIII. The IL-2 Receptor Regulation of T Cell Growth

IX. IL-2 Stimulates T Cell G1 Progression and c-myb Expression

X. Conclusions

References

2. Characteristics of Natural and Recombinant Human Interleukin 2

I. Introduction

II. Natural IL-2 Derived from Human PBL

III. Recombinant IL-2 Derived from E. coli

IV. Comparison of Biological Activities for Natural and Recombinant IL-2

V. Summary and Conclusions

References

3. Interleukin 2: Approaches to Structure Determination

I. Introduction

II. Preliminary Data

III. Species Homology

IV. Antibodies as Structure Probes

V. Recombinant DNA-Derived Proteins and Site-Directed Mutagenesis

VI. Peptide Synthesis

VII. Molecular Modeling and Graphics

VIII. Conclusion

References

4. Regulation of Interleukin 2 Production by the T Cell Antigen Receptor

I. Introduction

II. The T3/Ti Complex: Obligate Coexpression of T3 with Ti

III. Jurkat as a Model for the Study of T3/Ti-Mediated Activation

IV. The Role of Increases in the Concentration of Cytoplasmic Free Ca2+ in T3/Ti-Mediated Signaling

V. T3/Ti-Mediated Turnover of Polyphosphoinositides

VI. T3/Ti Activates Protein Kinase C

VII. Cholera Toxin Inhibits T3/Ti-Mediated Polyphosphoinositide Turnover

VIII. Induction of IL-2 Transcripts Requires Sustained T3/Ti-Ligand Interactions

IX. Summary and Future Directions

References

5. New Perspectives on the Structure of the Human High-Affinity Interleukin 2 Receptor

I. Introduction

II. Characterization of the Human IL-2 Receptor (Tac Antigen)

III. High- and Low-Affinity Forms of the IL-2 Receptor

IV. Expression of the Tac cDNA in Eukaryotic Cells

V. Structural Analysis of the High-Affinity IL-2 Receptor

References

6. Transmembrane Signaling by Interleukin 2

I. Introduction

II. Transmembrane Events in IL-2-Induced Proliferation

III. Delayed Events

IV. Oncogene Expression

V. Discussion

References

7. Mechanisms of Interleukin 2 Action: IL-2-Inducible Gene Expression in T Lymphocytes

I. Introduction

II. Early Molecular Events Associated with the Interaction of IL-2 and IL-2 Receptor: Potential Involvement of Protein Kinase C and Calcium

III. Rationale for Investigating the Expression of Protooncogenes and Other Genes in IL-2-Stimulated T Lymphocytes

IV. IL-2-Inducible Expression of Genes in Activated T Lymphocytes

V. Some Possible Explanations for the Patterns of Gene Expression Induced by IL-2, Phorbol Esters, and Mitogenic Lectins in Activated T Lymphocytes

VI. Mechanisms of IL-2-Mediated Gene Expression

VII. IL-2-Mediated Signal Transduction: Speculations and Future Directions

References

8. Interleukin 2 Binding Induces Transcription of a Novel Set of Genes: Implications for T Lymphocyte Population Dynamics

I. Introduction

II. Modes of IL-2 Induction

III. Mechanics of IL-2 Action

IV. Measures of IL-2 Responsiveness

V Significance of Positive IL-2 Receptor Regulation

VI. Conclusion

References

9. Abnormal Interleukin 2 Receptor Expression in Adult T Cell Leukemia

I. Introduction

II. Development of Anti-Tac Monoclonal Antibody

III. Identification of Anti-Tac Antibody as an Anti-IL-2 Receptor Antibody

IV. Characterization of IL-2 Receptor

V. IL-2R Expression in B Cells

VI. IL-2R Expression in ATL

VII. HTLV-I Infection and IL-2R Expression

VIII. Possible Role of IL-2 Receptor in the Leukemogenesis of ATL

IX. IL-2R Expression in T Cell Chronic Lymphocytic Leukemia

X. Summary

References

10. Interleukin 2 Receptor Inducers: Pathological Roles in Adult T Cell Leukemia

I. Introduction

II. Studies of IL-2R and ATL

III. Properties of Human IL-2R Protein

IV. Cloning of IL-2R Gene

V. Humoral Control of IL-2R Expression

VI. Abnormal Regulation of IL-2R Expression in ATL

VII. ADF Inducing IL-2R Expression

VIII. IL-2-Dependent and -Independent ATL: Stepwise Progression Model

IX. Possible Roles of IL-2R Dysregulation in ATL

X. Conclusion

References

11. Interleukin 2 Receptor-Directed Immunosuppressive Therapy

I. Introduction

II. Effect of M7/20 Treatment on Murine Cardiac Allografts

III. Effect of M7/20 Treatment of Murine Skin Allografts

IV. Effect of M7/20 and Anti-L3T4 Antibodies on Delayed-Type Hypersensitivity (DTH): The Role of Complement and Epitope

V. Effect of M7/20 Anti-IL-2R Antibody on Murine Autoimmunity: Diabetes Mellitus and Systemic Lupus Erythematosus Models

VI. Effect of ART18 Anti-IL-2R Antibody Treatment on Rat Cardiac Allografts

VII. Synergistic Effect of Anti-IL-2R mAb and Cyclosporin (CsA) Treatment

VIII. Effect of Anti-IL-2R on Graft Infiltration

IX. Effect of ART18 Treatment on Host Alloreactivity

X. Effect of ART18 Therapy on Pancreatic Islet Allografts

XI. Anti-IL-2R mAb Treatment of Subhuman and Human Primate Recipients of Kidney Allografts

XII. Development of a Recombinant IL-2 Toxin by Gene Fusion Technique

XIII. Discussion

References

12. Interleukin 2 as a Pharmacologic Reagent

I. Introduction

II. Rationale for the Use of IL-2 In Vivo

III. Immunotherapeutic Effects of IL-2 in Murine Models

IV. Human Studies of IL-2 Administration

V. Summary and Conclusions

References

Index