Table Of ContentImmunobiology
of
Natural Killer
Cells
Volume II
Editor
Eva Lotzova, Ph.D.
Department of General Surgery
University of Texas System Cancer Center
M.D. Anderson Hospital and Tumor Institute
Houston, Texas
Associate Editor
Ronald B. Herberman, M.D.
Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania
Boca Raton London New York
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This book is dedicated to the memory of my Mother
Eva Lotzova
PREFACE
It has become increasingly evident that natural killer (NK) cells may play an impor-
tant role in defense against neoplasias and against exogenous intruders, such as viruses,
bacteria, and parasites. More recent evidence also indicates involvement of NK cells in
several other biological phenomena. For instance, NK cells were demonstrated to reg-
ulate growth and functions of lymphocytes, and to control proliferation and differen-
tiation of myeloid and erythroid series of hemopoietic cells as well as pluripotential
stem cells. Even though the mechanism of the effects of NK cells on hemopoiesis and
lymphopoiesis has as yet not been elucidated, such regulation may be mediated by
various soluble biological substances which are produced by NK cells. These are ex-
emplified by different species of interferon, T cell and B cell growth factors, and col-
ony-stimulating factor. It is quite plausible that NK cells, via their ability to regulate
this wide array of biological functions, may represent a major component sustaining
homeostasis of the organism. The early appearance of NK cells in phylogenetic devel-
opment and their conservation through evolution to man, certainly supports this pos-
tulation.
Importantly, NK cells may have also a clinical relevance in cancer, nonmalignant
diseases, and in the field of bone marrow transplantation. Available evidence indicates
that the level of activity of these cells could be of prognostic value in relapse of leuke-
mia or in assessing the severity of graft-vs.-host disease after allogeneic bone marrow
transplantation, and perhaps these cells also may play a role in bone marrow graft
rejection, benign hemopathies, and regulation of autoimmunity. There are also sug-
gestions that NK cells may be therapeutically effective in cancer after their propagation
in vitro.
The possible importance of NK cells in biology and medicine led us to review for the
first time comprehensively various aspects of NK cells in a form of a book. This book
will be composed of two volumes, and will include the techniques for NK cell quanti-
fication and characterization; the phylogeny and ontogeny of NK cells; the genetics of
NK cell activity and the mechanisms of their functions; down- and up-regulation of
NK cell activity; NK cell-suppressor cell relationships; and propagation and cloning of
NK cells in vitro. We have also reviewed the cytotoxic profile of NK cells in cancer
patients and its modulation by biological response modifying agents.
We hope that this book will contribute to the advancing knowledge of readers in the
field of NK cells, and will be helpful as a teaching device. Furthermore, we trust that
this publication will stimulate further research in this interesting and important field.
Eva Lotzova, Editor
Ronald B. Herberman, Associate Editor
THE EDITORS
Dr. Eva Lotzova is Professor of Immunology, Chief of the Division of Immunoge-
netics at the University of Texas System Cancer Center, M.D. Anderson Hospital and
Tumor Institute, Houston. She is also Professor at the Graduate School of Biomedical
Sciences, The University of Texas, Houston. Dr. Lotzova received her M.S. and Ph.D.
degrees from Charles University, Prague, Czechoslovakia. She has been on the edito-
rial boards of several scientific journals and is Editor-in-Chief of the journal Natural
Immunity and Cell Growth Regulation. Furthermore, she is a contributing author to
CRC Press and Academic Press Scientific Book Series. She has been a consultant to
several governmental and private institutions in the area of biological response modi-
fication. Dr. Lotzova has been internationally recognized through her contributions to
the fields of experimental bone marrow transplantation, natural cell-mediated immu-
nity, and immunomodulation. She has contributed more than 150 publications to the
scientific literature and is a member of several scientific organizations including the
American Association of Immunologists, American Association for Cancer Research,
Transplantation Society, and International Society for Experimental Hematology.
Dr. Ronald B. Herberman, formerly Chief of the Biological Therapeutics Branch,
and Acting Associate Director for the Biological Response Modifiers Program, Divi-
sion of Cancer Treatment, National Cancer Institute, Frederick, Maryland, has re-
cently moved to Pittsburgh to become the first Director of the Pittsburgh Cancer In-
stitute. Dr. Herberman received B.A. and M.D. degrees from New York University,
graduating summa cum laude. After internship and residency in internal medicine at
the Massachusetts General Hospital, Boston, Dr. Herberman joined the National Can-
cer Institute as a clinical associate in the Immunology Branch in 1966. He then held a
series of positions at the National Cancer Institute, including Chief of the Laboratory
of Immunodiagnosis. Dr. Herberman is a Diplomate of the American Board of Inter-
nal Medicine and is past president of the Reticuloendothelial Society. He has been or
is currently on the editorial boards of a wide variety of oncology and immunology
journals, including Journal of Immunology, Cancer Research, Cellular Immunology,
Journal of the National Cancer Institute, and Natural Immunity and Cell Growth Reg-
ulation. He has published more than 600 papers in the fields of oncology and immu-
nology and is the author of books on Immunodiagnosis of Cancer, Natural Cell-Me-
diated Immunity Against Tumors, and NK Cells and Other Natural Effector Cells.
CONTRIBUTORS
Paola Allavena Carlos Lopez
Istituto “Mario Negri” Chief, Viral Exanthems and Herpesvirus
Milan, Italy Branch
Division of Virus Diseases
Colin G. Brooks Center for Infectious Diseases
Associate Centers for Disease Control
Program in Basic Immunology Atlanta, Georgia
Fred Hutchinson Cancer Research Center
Seattle, Washington Eva Lotzova
Professor of Immunology
J. Y. Djeu Department of General Surgery
Department of Medical Microbiology Section of Immunogenetics
College of Medicine The University of Texas System Cancer
University of South Florida Center
Tampa, Florida M. D. Anderson Hospital and Tumor
Institute
Patricia A. Fitzgerald
Houston, Texas
Assistant Professor
Department of Pathology
Jean E. Merrill
University of Medicine and Dentistry
Assistant Professor
of New Jersey—New Jersey
Department of Neurology
Medical School
UCLA School of Medicine
Newark, New Jersey
Los Angeles, California
Sidney H. Golub
Peter M. Moy
Professor
Surgical Oncology Fellow
Department of Surgery/Oncology
John Wayne Cancer Clinic
UCLA School of Medicine
Division of Surgical Oncology
Los Angeles, California
Department of Surgery
UCLA School of Medicine
Nabil Hanna
Los Angeles, California
Director
Department of Immunology and
Antiinfectives Therapy Andrew V. Muchmore
Smith Kline and French Laboratories Senior Investigator
Philadelphia, Pennsylvania Metabolism Branch
National Cancer Institute
Ronald B. Herberman Frederick Cancer Research Facility
Director Frederick, Maryland
Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania Joost J. Oppenheim
Laboratory of Molecular
T. Kasahara Immunoregulation
Department of Medical Biology and Biological Response Modifiers Program
Parasitology National Cancer Institute
Jichi Medical School Frederick Cancer Research Facility
Tochigi-Ken, Japan Frederick, Maryland
John R. Ortaldo Cherylyn A. Savary
Acting Chief Research Associate
Biological Therapeutics Branch Department of General Surgery
National Cancer Institute Section of Immunogenetics
Frederick Cancer Research Facility The University of Texas System Cancer
Frederick, Maryland Center
M. D. Anderson Hospital and Tumor
Institute
Hugh F. Pross Houston, Texas
Professor
Departments of Radiation Oncology and Giuseppe Scala
Microbiology and Immunology I Istituto di Scienze Biochimiche
Queen’s University II Facolta di Medicina, Napoli
Kingston, Ontario, Canada Naples, Italy
IMMUNOBIOLOGY OF NATURAL KILLER CELLS
Volume I
Assays for NK Cell Cytotoxicity; Their Values and Pitfalls
Separation and Characterization of Phenotypically Distinct Subsets of NK Cells
Ultrastructure and Cytochemistry of the Human Large Granular Lymphocytes
Phylogeny and Ontogeny of NK Cells
Tissue and Organ Distribution of NK Cells
Genetic Control of NK Cell Activity in Rodents
Phenotype, Functional Heterogeneity, and Lineage of Natural Killer Cells
Target Cell Structures, Recognition Sites, and the Mechanism of NK Cytotoxicity
Natural Killer Cytotoxic Factors (NKCF) Role in Cell-Mediated Cytotoxicity
Characteristics of Cultured NK Cells
Lectin-Dependent Killer Cells
MLC-Induced Cytotoxicity as a Model for the Development and Regulation of
NK Cytotoxicity
LGL Lymphoproliferative Diseases in Man and Experimental Animals: The
Characteristics of These Cells and Their Potential Experimental Uses
Volume II
In Vivo Activities of NK Cells Against Primary and Metastatic Tumors
in Experimental Animals
The Involvement of Natural Killer Cells in Human Malignant Disease
Impaired NK Cell Profile in Leukemia Patients
In Vivo Modulation of NK Activity in Cancer Patients
The Implications of Aberrant Natural Killer (MK) Cell Activity in
Nonmalignant Chronic Diseases
NK Cell Role in Regulation of the Growth and Functions of Hemopoietic and
Lymphoid Cells
Natural Killer Cells Active Against Viral, Bacterial, Protozoan, and Fungal Infections
Cytokine Secretion and Noncytotoxic Functions of Human Large
Granular Lymphocytes
Augmentation of Natural Killer Activity
Regulation of NK Cell Activity by Suppressor Cells
NK Cell Cloning Technology and Characteristics of NK Cell Clones
A Comparison of Antibody-Dependent Cellular Cytotoxicity (ADCC) and NK Activity
TABLE OF CONTENTS
Volume II
Chapter 1
In Vivo Activities of NK Cells Against Primary and Metastatic Tumors in
Experimental Animals.................................................................................................................. 1
Nabil Hanna
Chapter 2
The Involvement of Natural Killer Cells in Human Malignant Disease.............................11
Hugh F. Pross
Chapter 3
Impaired NK Cell Profile in Leukemia Patients.....................................................................29
Eva Lotzova, Cherylyn A. Savary, and Ronald B. Herberman
Chapter 4
In Vivo Modulation of NK Activity in Cancer Patients......................................................55
Peter M. Moy and Sidney H. Golub
Chapter 5
The Implications of Aberrant Natural Killer (NK) Cell Activity in
Nonmalignant Chronic Diseases....................... 75
Jean E. Merrill
Chapter 6
NK Cell Role in Regulation of the Growth and Functions of Hemopoietic and
Lymphoid Cells............................................................................................................................89
Eva Lotzova
Chapter 7
Natural Killer Cells Active Against Viral, Bacterial, Protozoan, and Fungal
Infections......................................................................................................................................107
Patricia A. Fitzgerald and Carlos Lopez
Chapter 8
Cytokine Secretion and Noncytotoxic Functions of Human Large Granular
Lymphocytes...............................................................................................................................133
Giuseppe Scala, J. Y. Djeu, Paola Allavena, T. Kasahara, John R. Ortaldo,
Ronald B. Herberman, and J. J. Oppenheim
Chapter 9
Augmentation of Natural Killer Activity................................................................................145
John R. Ortaldo and Ronald B. Herberman
Chapter 10
Regulation of NK Cell Activity by Suppressor Cells..............................................................163
Eva Lotzova and Cherylyn A. Savary
