Table Of ContentMechanisms of Cytotoxicity
by NK Cells
Edited by
Ronald B. Herberman
Biological Therapeutics Branch
Biological Response Modifiers Program
National Cancer Institute
National Institutes of Health
Frederick Maryland
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Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
E. W. Ades (231), Department of Immunology Research, Lilly Research Laborator-
ies, Indianapolis, Indiana 46268
Paola Allavena (617), Biological Therapeutics Branch, Biological Response Modi-
fiers Program, DCT, NCI-Frederick Cancer Research Facility, Frederick,
Maryland 21701
Sumio Arai (489), Department of Laboratory Medicine, Kumamoto University
Medical School, Kumamoto, Japan
Emira Ayroldi (421), Institute of Pharmacology, University of Perugia, Perugia,
Italy
Theodore F. Beals (195), Department of Pathology, University of Michigan Veterans
Administration Medical Center, Ann Arbor, Michigan 48109
J. G. Bekesi (117), Department öf Neoplastic Diseases, Mount Sinai Medical School,
New York, New York 10029
Philip J. Bierman (465), Experimental Immunology Laboratory, Department of
Internal Medicine, Veterans Administration Medical Center and the University
of Nebraska Medical Center, Omaha, Nebraska 68101
Isaac Bianca (335), Biological Response Modifiers Program, National Cancer
Institute, Frederick Cancer Research Facility, Frederick, Maryland 21701
Robert Blumenthal (305), Laboratory of Theoretical Biology, NCI, National Insti-
tutes of Health, Bethesda, Maryland 20205
Reinder L. H. Bolhuis (543, 631), Rotterdam Radio-Therepeutic Institute, Rotter-
dam and Radiobiologieal Institute TNO, Rijswijk, The Netherlands
Benjamin Bonavida (323, 477), Department of Microbiology and Immunology,
UCLA School of Medicine, Los Angeles, California 91701
Claudio Bordignon (93), Department of Pathology, State University of New York at
Buffalo, Buffalo, New York 14214
Colin G. Brooks (245, 263, 645), Basic Immunology, Fred Hutchinson Cancer
Research Center, Seattle, Washington 98104
Michael J. Brunda (397), Department of Experimental and Applied Biology, Roche
Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110
xiii
XIV Contributors
Gordon F. Burns (589), Lions Clinical Cancer Research Laboratory, Clinical Re-
search Unit of the Walter and Eliza Hall Institute of Medical Research, Mel-
bourne, Victoria, Australia
Denis M. Callewaert (17, 381), Department of Chemistry, Oakland University,
Rochester, Michigan 48063
Kathleen Carine (213), UC San Diego Cancer Center, University of California, San
Diego, La Jolla, California 92093
Olli Carpen (185), Department of Pathology, University of Helsinki, Helsinki,
Finland
William H. Chambers (351), Division of Oncology, Department of Medicine, Van-
derbilt University, Nashville, Tennessee 37203
Allan R. Chen (287), Division of Immunology, Duke University Medical Center,
Durham, North Carolina 27706
M. Culwell (231), Department of Immunology Research, Lilly Research Laborator-
ies, Indianapolis, Indiana 46268
John P. Daley (93), Department of Pathology, State University of New York at
Buffalo, Buffalo, New York 14214
Viveca Davatelis (397), Department of Experimental and Applied Biology, Roche
Research Center, Hoffmann-La Roche Inc., Nutley, New Jersey 07110
Richard L. Deem (155), Geriatric Research, Education and Clinical Center, Wads-
worth VA Medical Center, Los Angeles, California and Departments of Medi-
cine, and Microbiology and Immunology, University of California, Los Angeles
School of Medicine, Los Angeles, California 90024
Gino Degliantoni (29), The Wistar Institute for Anatomy and Biology, Philadelphia,
Pennsylvania 19104
Günther Dennert (173), Comprehensive Cancer Center, University of Southern
California, School of Medicine, Los Angeles, California 90033
Patricia A. Fitzgerald (125), Laboratory of Herpesvirus Infections, Memorial
Sloan-Kettering Institute for Cancer Research, New York, New York
James T. Forbes (351), Division of Oncology, Department of Medicine, Vanderbilt
University, Nashville, Tennessee 37203
Guido Forni (433), Istituto di Microbiologia Universität, degli Studi di Torino,
Turin, Italy
Luigi Frati (433), Istituto di Patologia Generale Universität, degli Studi "La
Sapienze", Rome, Italy
Yoshiaki Fujimiya (521), Departments of Pathology and Microbiology, University of
Southern California School of Medicine, Los Angeles, California 90007
Antonio Giampietri (421), Institute of Pharmacology, University of Perugia, Peru-
gia, Italy
Ronald H. Goldfarb (137, 205, 263), Department of Immunology and Infectious
Disease, Central Research Division, Pfizer, Inc., Groton, Connecticut
R. J. van de Griend (631), Rotterdam Radio-Therepeutic Institute, Rotterdam and
Radiobiological Institute TNO, Rijswijk, The Netherlands
Maryanna Henkart (305), Immunology Branch, NCI, National Institutes of Health,
Bethesda, Maryland 20205
Contributors XV
Pierre Henkart (305), Immunology Branch, NCI, National Institutes of Health,
Bethesda, Maryland 20205
Ronald B. Herberman (1, 335, 421, 433, 617), Biological Therapeutics, Biological
Response Modifiers Program, DCT, National Cancer Institute, Frederick
Cancer Research Facility, Frederick, Maryland 21701
J. P. Hester (507), Department of Hematology, The University of Texas System
Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, Texas
A. Hinson (231), Department of Immunology Research, Lilly Research Laborator-
ies, Indianapolis, Indiana 46268
JohnC. Hiserodt (195), Department of Pathology, University of Michigan, Veterans
Administration Medical Center, Ann Arbor, Michigan 48109
Dorothy Hudig (71, 213), Department of Microbiology, School of Medicine, Uni-
versity of Nevada, Reno, Nevada 89507
Margot M. Ip (253), Grace Cancer Drug Center, Roswell Park Memorial Institute,
Buffalo, New York
Donald R. Johnson (361), Department of Pathology and Laboratory Medicine,
Department of Microbiology and Eppley Institute for Research on Cancer and
Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska,
68105
Joseph Kaplan (61, 103), Department of Pediatrics, Wayne State University School of
Medicine, Detroit, Michigan 48201
Klas Karre (81), Department of Tumor Biology, Karolinska Institute, S-104 01
Stockholm, Sweden
H. David Kay (263, 465), Experimental Immunology Laboratory, Department of
Internal Medicine, Veterans Administration Medical Center and the University
of Nebraska Medical Center, Omaha, Nebraska 68105
M. J. Keating (507), Department of Hematology, The University of Texas System
Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston, Texas
Tatsuo Kiyohara (223), Department of Microbiology and Immunology, Queen s
University, Kingston, Ontario, Canada
Lynell W. Klassen (465), Experimental Immunology Laboratory, Department of
Internal Medicine, Veterans Administration Medical Center, and the University
of Nebraska Medical Center, Omaha, Nebraska 68105
Eva Klein (443), Department of Tumor Biology, Karolinska Institutet, S-104 01
Stockholm, Sweden
Michiko Kobayashi (29), The Wistar Institute for Anatomy and Biology, Phil-
adelphia, Pennsylvania 19104
Hillel S. Koren (253, 287, 373, 607), Department ofMicrobiology and Immunology,
Duke University Medical Center, Durham, North Carolina 27706
Katsuo Kumagai (489), Department of Microbiology, Tohoku University, School of
Dentistry, Sendai, Japan
Abraham Kupfer (173), Department of Biology, University of California, San Diego,
La Jolla, California 92093
Lewis L. Lanier (563), Becton Dickinson Monoclonal Center, Inc., Mountain View,
California 94043
XVI Contributors
Edmund C. Lattime (409), Immunobiology Program, Memorial Sloan-Kettering
Cancer Center, New York, New York
Robert J. Lauzon (223), Department of Microbiology and Immunology, Queen s
University, Kingston, Ontario, Canada
KamH. Leung1 (253), Grace Cancer Drug Center, Roswell Park Memorial Institute,
Buffalo, New York
T. Juhani Linna (49), Central Research and Development Department, Glenolden
Laboratory, E.I. du Pont de Nemours and Company, Glenolden, Pennsylvania
Lucille London (29), The Wistar Institute for Anatomy and Biology, Philadelphia,
Pennsylvania 19104
Carlos Lopez (125), Laboratory of Herpesvirus Infections, Memorial Sloan-
Kettering Institute for Cancer Research, New York, New York
E. Lotzovä (507), Laboratory of I mmuno genetics, Department of General Surgery,
The University of Texas System Cancer Center, M.D. Anderson Hospital and
Tumor Institute, Houston, Texas
Stuart Macphail (409), Immunobiology Program, Memorial Sloan-Kettering Cancer
Center, New York, New York
Norma H. Mahle (381), Department of Chemistry, Oakland University, Rochester,
Michigan 48063
E. J. Margalioth (117), Department of Obstetrics and Gynecology, Hadassh Uni-
versity Hospital, Jerusalem, Israel
Llewellyn Mason (617), Biological Therapeutics Branch, Biological Response Mod-
ifiers Program, DCT, NCI-Frederick Cancer Research Facility, Frederick,
Maryland 21701
Maria-Grazia Masucci (443), Department of Tumor Biology, Karolinska Institutet,
S-104 01 Stockholm, Sweden
Graziella Migliorati (421), Institute of Pharmacology, University of Perugia, Peru-
gia, Italy
Paul Millard (305), Immunology Branch, NCI, National Institutes of Health, Be-
thesda, Maryland 20205
Lory Minning (71, 213), UC Cancer Center, University of California, San Diego, La
Jolla, California 92093
Madhavan P. N. Nair (453), Departments of Pediatrics and Epidemiology, The
University of Michigan, Ann Arbor, Michigan 48109
Ichiro Nakamura (93), Department of Pathology, State University of New York at
Buffalo, Buffalo, New York 14214
Walter Newman (655), Department of Molecular Immunology, Ortho Pharmaceuti-
cal Corporation, Raritan, New Jersey 08869
Thomas Oeltmann (351), Division of Oncology, Department of Medicine, Vanderbilt
University, Nashville, Tennessee 37203
'Present address: Central Research and Development Department, Glenolden Laboratory, E. I. du Pont
de Nemours and Company, Glenolden, Pennsylvania.
Contributors XVll
John R. Ortaldo (335, 617), Biological Response Modifiers Program, DCT, National
Cancer Institute-Frederick Cancer Research Facility, Frederick, Maryland
21701
Mahadev R. Patel (49), Central Research and Development Department, Glenolden
Laboratory, E.I. du Pont de Nemours and Company, Glenolden, Pennsylvania
Paul K. Pattengale (521), Departments of Pathology and Microbiology, University of
Southern California, School of Medicine, Los Angeles, California 90007
Graham Pawelec (655), Immunology Laboratory, Medizinische Klinik, D-7400
Tübingen, West Germany
Peter Pereira (499), Department of Biological Structure, University of Washington,
Seattle, Washington 98105
Bice Perussia (29), The Wistar Institute for Anatomy and Biology, Philadelphia,
Pennsylvania 19104
Howard T. Petrie (465), Experimental Immunology Laboratory, Department of
Internal Medicine, Veterans Administration Medical Center and the University
of Nebraska Medical Center, Omaha, Nebraska 68101
Joseph H. Phillips (563), Becton Dickinson Monoclonal Center, Inc., Mountain
View, California 94043
Mario Piccoli (433), Istituto di Patologia Generale Universita, degli Studi "La
Sapienze", Rome, Italy
Sylvia B. Pollack (39, 499), Department of Biological Structure, University of
Washington, Seattle, Washington 98105
Hugh F. Pross (529), Departments of Radiation Oncology and Microbiology and
immunology, Queen's University at Kingston, Ontario, Canada
Oscar Ramos (443), Department of Tumor Biology, Karolinska lnstitutet, S-104 01
Stockholm, Sweden
Doug Redelman (213), Department of Microbiology, School of Medicine, University
of Nevada, Reno, Navada 89507
Craig Reynolds (305), Biological Therapeutics Branch, NCI, Frederick Cancer
Research Facility, Frederick, Maryland 21701
Carlo Riccardi (421), Institute of Pharmacology, University of Perugia, Perugia,
Italy
Claire P. Robles (499), Department of Biological Structure, University of Washing-
ton, Seattle, Washington 98105
John C. Roder (223), Department of Microbiology and Immunology, Queen s
University, Kingston, Ontario, Canada
Robert C. Roozemond (477), Laboratory of Histology and Cell Biology, University
of Amsterdam, Amsterdam, The Netherlands
Eero Saksela (185), Department of Pathology, University of Helsinki, Finland
Angela Santoni (433), Istituto di Patologia Generale Universita, degli Studi "La
Sapienze', Rome, Italy
C. A. Savary (507), Laboratory of Immunogenetics, Department of General
Surgery, The University of Texas System Cancer Center, M.D. Anderson Hos-
pital and Tumor Institute, Houston, Texas
XV111 Contributors
Thomas E. Schindler2 (125), Laboratory of Herpesvirus Infections, Memorial
Sloan-Kettering Institute for Cancer Research, New York, New York
M. Schlesinger (117), Hubert H. Humphrey Center for Experimental Medicine and
Cancer Research, The Hebrew University, Hadassh Medical School, Jeru-
salem, Israel
Stanley A. Schwartz (453), Departments of Pediatrics and Epidemiology, The
University of Michigan, Ann Arbor, Michigan 48109
William Seaman (245), Department of Medicine, VA Medical Center and University
of California, San Francisco, California, 94143
J. S. Singer (173), Department of Biology, University of California, San Diego, La
Jolla, California 92093
Osias Stutman (409), Immunobiology Program, Memorial Sloan-Kettering Cancer
Center, New York, New York
Ryuji Suzuki (489), Department of Microbiology, Tohoku University, School of
Dentistry, Sendai, Japan
Satsuki Suzuki (489), Department of Microbiology, Tohoku University, School of
Dentistry, Sendai, Japan
Stephan Targan (155), Geriatric Research, Education and Clinical Center, Wads-
worth VA Medical Center, Los Angeles, California and Departments of Medi-
cine, and Microbiology and Immunology, University of California, Los Angeles
School of Medicine, Los Angeles, California 90024
Tuomo Timonen (599), Department of Pathology, University of Helsinki, Helsinki,
Finland
William W. Travis3 (607), Division of Immunology, Duke University Medical Cen-
ter, Durham, North Carolina 27706
Tony Triglia (589), Lions Clinical Cancer Research Laboratory, Clinical Research
Unit of the Walter and Eliza Hall Institute of Medical Research, Melbourne,
Victoria, Australia
Giorgio Trinchieri (29), The Wistar Institute for Anatomy and Biology, Philadelphia,
Pennsylvania 19104
Ismo Virtanen (185), Department of Pathology, University of Helsinki, Finland
Elizabeth A. Wayner (263), Basic Immunology, Fred Hutchinson Cancer Research
Center, Seattle, Washington 98104
Monica Weitzen (477), Department of Microbiology and Immunology, UCLA School
of Medicine, Los Angeles, California 21701
2Present address: Xytronyx, Inc., 10 West 35th Street, Chicago, Illinois 60616.
3Present address: Department of Microbiology and Immunology, Baylor College of Medicine, Hous-
ton, Texas 77030.
4Present address: The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
Contributors XIX
Jerome A. Werkmeister (529, 589), Departments of Radiation and Oncology and
Microbiology and Immunology, Queen's University at Kingston, Ontario,
Canada and Clinical Research Unit of the Walter and Eliza Hall Institute of
Medical Research, Melbourne, Victoria, Australia
Peter Wernet (655), Immunology Laboratory, Medizinsche Klinik, D-7400 Tu-
bingen, West Germany
Stanley M. Wilbur (323), Department of Microbiology and Immunology, UCLA
School of Medicine, Los Angeles, California 21701
Janet Woodcock (245), Department of Medicine, VA Medical Center and University
of California, San Francisco, California 94143
Pascale Wortley (499), Department of Biological Structure, University of Washing-
ton, Seattle, Washington 98105
Susan C. Wright (323), Department of Microbiology and Immunology, UCLA School
of Medicine, Los Angeles, California 21701
Preface
About a dozen years have elapsed since the first reports appeared of cytotoxic
reactivity of lymphocytes from normal donors against tumor cell lines. While the
phenomenon of natural cytotoxicity was at first considered by many immunologists to
be an in vitro artifact and for several years was only studied by a few investigators,
recent rapid advances in our understanding of these cells, coupled with mounting
evidence for multiple in vivo functions, have catapulted work on NK cells into a
major aspect of modern immunological research. In addition to their likely role in
antitumor defenses, NK cells appear to play an important role in natural resistance to
some viral and other microbial infections, in rejection of bone marrow transplants,
and in regulation of other immune responses, including antibody production.
Increasing suggestions for the in vivo importance of NK cells, along with rapid
advances in the ability to purify and characterize NK cells, have stimulated the
interest of increasing numbers of immunologists as well as scientists from other
disciplines who, in turn, have applied new techniques to further enhance our under-
standing of these cells and their functions. There have also been parallel advances in
our insight in other natural effector cells, which also may make important contribu-
tions to natural immunity against disease. The availability of highly purified popula-
tions of effector cells, of monoclonal antibodies reactive with them, and of
homogenous recombinant cytokines that affect their reactivity has led to particularly
impressive progress in our understanding of the mechanism(s) by which NK cells lyse
susceptible target cells and of the mechanisms of the regulation of NK activity.
Attempts to help the scientific community stay abreast of the latest developments in
this field have led to the publication of several review articles on different aspects of
natural cell-mediated immunity, and up-to-date detailed summaries of findings from
leading investigators in the field have been compiled in two major volumes: ''Natural
Cell-Mediated Immunity against Tumors" (R. B. Herberman, editor; Academic
Press Inc., 1980) and "NK Cells and Other Natural Effector Cells" (R. B. Herber-
man, editor; Academic Press, Inc., 1982). The length of the latter work (over 1500
pages) and the continued rapid increase in the number of relevant publications in
peer-reviewed journals attest to the fact that work in this field has become so extensive
that it can no longer be adequately reported in breadth as well as depth. This volume is
based on an international workshop on these topics, devoted to an extensive summary
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