Riethm?ller / Wernet / Cudkowicz Natural and Induced Cell-Mediated Cytotoxicity

Effector and Regulatory Mechanisms
1. Auflage 2014
ISBN: 978-1-4832-6982-5
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 256 Seiten

Natural and Induced Cell-Mediated Cytotoxicity: Effector and Regulatory Mechanisms contains the proceedings of the Erwin Riesch Symposium organized on the occasion of the Fifth Centennial of the University of T?bingen in Germany on October 20-23, 1977. The symposium provided a forum for reviewing the progress that has been made in understanding the effector and regulatory mechanisms underlying natural and induced cell-mediated cytotoxicity. Topics covered range from the immunobiology of natural killer cells to the role of macrophages as regulator, accessory, and effector cells in cytotoxicity. Comprised of 27 chapters, this book begins by analyzing the characteristics of natural cytotoxic cells in mice, followed by a discussion on the generation in vivo of mouse natural cytotoxic cells and the role of cytotoxic T cells in the local defense against solid tumors. Subsequent chapters focus on the natural cytotoxicity of human lymphocytes; opposing effects of interferon on natural killer and target cells; susceptibility of cloned melanoma to natural cytotoxicity; and cell-mediated immunity against avian virus-induced tumor cells. The book also examines alternative routes of entry for cell surface antigens into the immune system before concluding with a chapter that considers interferon induction by Corynebacterium parvum. This monograph should be of value to students, researchers, and practitioners in the fields of biology and immunology.

Autoren/Hrsg.

Riethmüller, Gert

Wernet, Peter

Cudkowicz, Gustavo

Inhaltsverzeichnis

1;Front Cover;1
2;Natural and Induced Cell-Mediated Cytotoxicity: Effector and Regulatory Mechanisms;4
3;Copyright Page;5
4;Table of Contents;6
5;CONFEREES;10
6;PREFACE;12
7;ACKNOWLEDGMENTS;14
8;PART 1: IMMUNOBIOLOGY OF NATURAL KILLER CELLS: MECHANISMS AND REGULATION IN THE MURINE SYSTEM;248
8.1;CHAPTER 1. CHARACTERISTICS OF NATURAL CYTOTOXIC CELLS IN
MICE;16
8.1.1;SPECIFICITY OF MOUSE NK CELLS;16
8.1.2;IN VITRO CHARACTERISTICS OF MOUSE NK CELLS;17
8.1.3;NONGENETIC FACTORS INFLUENCING NK ACTIVITY;17
8.1.4;GENETIC REGULATION OF NK ACTIVITY;19
8.1.5;References;19
8.2;CHAPTER 2. GENERATION IN VIVO OF MOUSE NATURAL CYTOTOXIC CELLS;22
8.2.1;GENERATION OF MOUSE NK CELLS IN VIVO;22
8.2.2;Acknowledgments;31
8.2.3;References;31
8.3;CHAPTER 3. ARE CYTOTOXIC T CELLS RELEVANT IN THE LOCAL
DEFENSE AGAINST SOLID TUMORS;34
8.3.1;T1699 TUMOR MODEL;35
8.3.2;MOLONEY SARCOMA
TUMORS–A/Sn MICE;37
8.3.3;CONCLUDING STATEMENT;41
8.3.4;Acknowledgments;41
8.3.5;References;41
9;PART 2: 1MMUNX)BIOLOGY OF NATURAL KILLER CELLS: NATURE OF EFFECTOR CELLS IN THE HUMAN SYSTEM;44
9.1;CHAPTER 4. NATURAL CYTOTOXICITY OF HUMAN LYMPHOCYTES. IMMUNOGLOBULIN DEPENDENT AND INDEPENDENT SYSTEMS;44
9.1.1;NATURAL CYTOTOXICITY DEPENDENT ON THE PRESENCE OF IMMUNOGLOBULIN;46
9.1.2;NATURAL CYTOTOXICITY NOT DEPENDENT ON IMMUNOGLOBULIN;48
9.1.3;CONCLUDING REMARKS;50
9.1.4;Acknowledgments;50
9.1.5;References;50
9.2;CHAPTER 5. CHARACTERIZATION OF EFFECTOR CELLS IN HUMAN NATURAL CYTOTOXICITY;52
9.2.1;METHODS;52
9.2.2;RESULTS AND DISCUSSION;53
9.2.3;Acknowledgments;57
9.2.4;References;57
9.3;CHAPTER 6. EFFECTOR CELLS OF NATURAL CYTOTOXICITY AGAINST HUMAN MELANOMA CELLS;58
9.3.1;MATERIALS AND METHODS;59
9.3.2;RESULTS;61
9.3.3;DISCUSSION;68
9.3.4;Acknowledgments;70
9.3.5;References;70
9.4;CHAPTER 7. RELATION OF EFFECTOR MECHANISMS TO TARGET CELL ORIGIN;72
9.4.1;CONCLUDING REMARKS;76
9.4.2;Acknowledgment;77
9.4.3;References;77
10;PART 3: MECHANISMS, TARGET CELLS, AND REGULATION OF NATURAL KILLER CELL ACTIVITY IN MAN;78
10.1;CHAPTER 8. MODELS FOR MECHANISMS OF NATURAL CYTOTOXICITY;78
10.1.1;PROBLEMS WITH A MODEL FOR NK IN WHICH K CELLS ARE ARMED WITH NATURAL ANTIBODIES VIA THE CLASSICAL FcR;79
10.1.2;MODEL NO. 1 : NATURAL ANTIBODIES ARM FcR2 ON
FcR1-FcR2-POSITIVE CELLS;84
10.1.3;MODEL NO. 2: NK DUE TO A SPECIFIC MEMBRANE RECEPTOR ON FcR-POSITIVE CELLS;84
10.1.4;MODEL NO. 3: IgG BOUND TO FcR TURNS ON OR AUGMENTS MECHANISMS OF NK REACTIVITY;85
10.1.5;CONCLUDING REMARKS;86
10.1.6;References;86
10.2;CHAPTER 9. OPPOSING EFFECTS OF INTERFERON ON NATURAL KILLER AND TARGET CELLS;90
10.2.1;Acknowledgments;96
10.2.2;References;96
10.3;CHAPTER 10. SPECIFICITY OF NATURAL CYTOTOXIC CELLS DETERMINED BY ANTIBODY;98
10.3.1;MATERIALS AND METHODS;99
10.3.2;RESULTS;99
10.3.3;CONCLUDING REMARKS;101
10.3.4;Acknowledgment;102
10.3.5;References;102
10.4;CHAPTER 11. MANIPULATIONS OF NATURAL CYTOTOXICITY IN TUMOR PATIENTS VIA BCG;104
10.4.1;MATERIALS AND METHODS;105
10.4.2;RESULTS;107
10.4.3;DISCUSSION;111
10.4.4;Acknowledgments;113
10.4.5;References;113
10.5;CHAPTER 12. SUSCEPTIBILITY OF CLONED MELANOMA TO NATURAL CYTOTOXICITY;114
10.5.1;MATERIAL AND METHODS;115
10.5.2;RESULTS;120
10.5.3;DISCUSSION;126
10.5.4;Acknowledgment;129
10.5.5;References;129
11;PART 4: INDUCED CELL-MEDIATED CYTOTOXICITY: TARGETS, MECHANISMS, AND CONCEPTS;132
11.1;CHAPTER 13. ANTIGEN RECOGNITION BY CYTOTOXIC T LYMPHOCYTES;132
11.1.1;CTL INTERACT WITH H-2K AND H-2D;134
11.1.2;SPECIFICITY OF ALLOANTIGEN-ACTIVATED CTL;135
11.1.3;CTL RECEPTOR MODELS;138
11.1.4;RUMINATIONS ON COMPONENTS OF CTL RECEPTORS;140
11.1.5;CONCLUDING STATEMENT;141
11.1.6;Acknowledgments;141
11.1.7;References;141
11.2;CHAPTER 14. GENERATION OF TNP-SPECIFIC H-2-RESTRICTED MURINE CYTOTOXIC CELLS AS A FUNCTION OF TNP-CELL SURFACE PRESENTATION;144
11.2.1;CONCLUDING STATEMENT;148
11.2.2;References;148
11.3;CHAPTER 15. SECONDARY SENDAI-SPECIFIC T-EFFECTOR CELLS: REQUIREMENTS FOR RESTIMULATION, TARGET CELLS RECOGNITION, AND LYSIS;150
11.3.1;RESULTS AND DISCUSSION;151
11.3.2;CONCLUSIONS;157
11.3.3;Acknowledgments;158
11.3.4;References;158
11.4;CHAPTER 16. CYTOTOXIC T LYMPHOCYTES INDUCED BY H-2 NEGATIVE STIMULATOR CELLS;160
11.4.1;RESULTS AND DISCUSSION;160
11.4.2;Acknowledgments;163
11.4.3;References;163
11.5;CHAPTER 17. CELL-MEDIATED IMMUNITY AGAINST AVIAN VIRUS-INDUCED TUMOR CELLS;166
11.5.1;RESULTS;167
11.5.2;CONCLUDING STATEMENT;169
11.5.3;Acknowledgments;170
11.5.4;References;170
11.6;CHAPTER 18. ALTERNATIVE ROUTES OF ENTRY FOR CELL SURFACE ANTIGENS INTO THE IMMUNE SYSTEM;172
11.6.1;LATENT HELP;174
11.6.2;THE RATES OF GENERATION OF K-SPECIFIC AND Ia-SPECIFIC HELP COMPARED;175
11.6.3;MHC-RESTRICTED Th CELLS;176
11.6.4;IMPLICATIONS FOR SELF-TOLERANCE AND AUTOIMMUNE DISEASE;177
11.6.5;References;178
12;PART 5: INDUCED CELL-MEDIATED CYTOTOXICITY: REACTIVITY AGAINST MODIFIED SELF IN MAN;180
12.1;CHAPTER 19. CELL-MEDIATED CYTOTOXICITY AGAINST TNP-MODIFIED HUMAN LEUKOCYTES;180
12.1.1;GENERAL CHARACTERISTICS OF THE HUMAN CYTOTOXIC RESPONSE TO SELF-TNP;180
12.1.2;ALLOGENEIC CROSS REACTIVITY IN TNP-CML;184
12.1.3;HLA RESTRICTED ACTIVITY IN TNP-CML;185
12.1.4;SD-ASSOCIATION OF ACTIVITY IN TNP-CML;187
12.1.5;DISCUSSION;188
12.1.6;References;189
12.2;CHAPTER 20. HLA RESTRICTION OF CYTOTOXICITY AGAINST INFLUENZA-INFECTED HUMAN CELLS;192
12.2.1;METHODS;192
12.2.2;RESULTS AND DISCUSSION;193
12.2.3;Acknowledgments;195
12.2.4;References;196
12.3;CHAPTER 21. SELF-RESTRICTED CYTOTOXICITY AGAINST ACUTE MYELOID LEUKEMIA CELLS;198
12.3.1;MATERIALS AND METHODS;198
12.3.2;RESULTS;200
12.3.3;DISCUSSION;202
12.3.4;CONCLUDING STATEMENT;204
13;PART 6: MACROPHAGES AS REGULATOR, ACCESSORY, AND EFFECTOR CELLS IN CYTOTOXICITY;206
13.1;CHAPTER 22. REGULATORY ROLE OF MACROPHAGES IN NORMAL AND NEOPLASTIC HEMOPOIESIS;206
13.1.1;Acknowledgment;212
13.1.2;References;212
13.2;CHAPTER 23. SERUM HEMATOPOIETIC INHIBITORS AND TUMOR NECROSIS FACTOR;214
13.2.1;METHODS;218
13.2.2;RESULTS AND DISCUSSION;219
13.2.3;References;221
13.3;CHAPTER 24. ROLE OF ADHERENT CELLS IN THE INDUCTION OF CYTOTOXIC T LYMPHOCYTES: PROMOTION, SUPPRESSION, AND ANTIGEN PRESENTATION;224
13.3.1;DEPRESSIVE EFFECTS OF ANTIMACROPHAGE AGENTS ON THE INDUCTION OF F1 ANTIPARENT CTL;225
13.3.2;DEPRESSIVE EFFECTS OF ADHERENT CELL REMOVAL ON THE INDUCTION OF F1 ANTIPARENT CTL;227
13.3.3;FUNCTIONAL RECONSTITUTION WITH PLASTIC-ADHERENT CELLS OF SPLENOCYTES RENDERED INCOMPETENT BY SEPHADEX G-10 FILTRATION;229
13.3.4;THE POTENT STIMULATOR ACTIVITY OF PARENTAL H-2Db PLASTIC-ADHERENT CELLS IS INFLUENCED BY THE H-2K REGION;230
13.3.5;SUPPRESSION OF CTL BY CARRAGEENAN-ACTWATED MACROPHAGELIKE CELLS;233
13.3.6;CONCLUDING REMARKS;234
13.3.7;Acknowledgments;234
13.3.8;References;234
13.4;CHAPTER 25. CYTOTOXICITY OF BONE MARROW MACROPHAGES FOR NORMAL AND MALIGNANT TARGETS;236
13.4.1;MATERIALS AND METHODS;236
13.4.2;RESULTS AND DISCUSSION;237
13.4.3;CONCLUDING STATEMENTS;241
13.4.4;References;241
13.5;CHAPTER 26. INTERFERON INDUCTION BY CORYNEBACTERIUM PARVUM;242
13.5.1;MATERIALS AND METHODS;242
13.5.2;RESULTS;243
13.5.3;DISCUSSION;246
13.5.4;References;247
14;PART 7: CONCLUSIONS AND
OVERVIEW;248
14.1;CHAPTER 27. RECAPITULATION AND ASSESSMENT
OF THE CONFERENCE DISCUSSIONS;248
14.1.1;FUNCTIONAL ROLE OF NK CELLS;249
14.1.2;NK VERSUS K CELL DISTINCTION;250
14.1.3;NATURE OF EFFECTOR CELLS;250
14.1.4;ONTOGENY AND REGULATION;252
14.1.5;RESTRICTED VERSUS NONRESTRICTED CTL AND AUTOREACTIVITY;253
14.1.6;MACROPHAGES;255
14.1.7;CODA;255
14.1.8;Acknowledgment;256
14.1.9;References;256

Leseproben

CHARACTERISTICS OF NATURAL CYTOTOXIC CELLS IN MICE

Rolf Kiessling

Publisher Summary

This chapter describes the characteristics of natural cytotoxic cells in mice. Several groups of investigators have shown that tumor cells can be destroyed by effector cells from normal donors who, as far as could be determined, had neither been immunized nor sensitized. These effector cells have been designated as natural killer (NK) cells in analogy with the phenomenon of natural antibodies. NK-cell phenomena have been studied in mice, rats, and man. Almost all studies have utilized the short term 51Cr release assay. In the case of rats and man, long-term assays, such as the microcytotoxic assays, have been employed. Target cells cultured are consistently more sensitive to NK lysis than the respective lines. It is now well established that in the mouse, the NK cell is not a mature T cell as it lacks detectable amounts of theta-antigen and inasmuch as nude mice exhibit high activity. Mouse NK cells lack surface immunoglobulin as well as C3 receptors.

Several groups of investigators have shown that tumor cells can be destroyed by effector cells from normal donors who, as far as could be determined, had neither been immunized nor sensitized. These effector cells have been designated NK, i.e., natural killer cells, in analogy with the phenomenon of natural antibodies. NK-cell phenomena have been studied in mice, rats, and man. Almost all studies have utilized the short term 51Cr release assay, and most of the experiments to be considered have been performed with this technique. In the case of rats and man, long-term assays, such as the microcytotoxic assays, have been employed.

SPECIFICITY OF MOUSE NK CELLS

It has been concluded by several groups of investigators that mouse NK cells show a reproducible pattern with respect to target cell sensitivity (1–4). T lymphomas constitute the tumor cell type most susceptible to NK lysis, but other tumors of nonhematopoietic origin also express significant lytic sensitivity (1,2). Susceptibility to lysis by NK cells depends on expression of relevant target structures on the various cell lines as verified in competition assays. In these assays the capacity of various “cold” competitor cells to inhibit isotope release from labeled target cells was assessed. A good correlation between susceptibility to direct lysis and the ability to inhibit lysis was generally found (1,2). NK-cell-mediated lysis was found to function across H-2 (1) or species barriers (5).

Target cells cultured are consistently more sensitive to NK lysis than the respective lines (1, 2). Following explantation of a mouse lymphoma, this increase in lysis sensitivity did not occur until after three weeks of culture.

A variety of cell surface components have been considered as the target site for the cytolytic activity of NK cells, but no compelling evidence is available to support any of the hypothetical explanations. The most widely supported notion suggested that NK activity is directed against endogenous C-type viral antigens on the target surface (2). However, Becker and Klein (6) found no correlation between the NK susceptibility of Moloney lymphoma sublines that differed markedly in Moloney virus-determined antigen expression. It is also noteworthy that mouse NK cells can kill certain human targets, T-cell lymphomas, in particular (5). Furthermore, human cell lines that were deliberately superinfected with mouse xenotropic C-type virus by passage in nude mice and subsequently tested for NK sensitivity showed no increase or altered sensitivity to mouse NK cells. Thus, the target specificity attacked by the NK cell remains unknown. It is of interest that recent evidence suggests that NK cells can play a role in resistance not only to certain tumor lines, but also to normal bone marrow grafts (7, 8). Accordingly, NK cells could also play a role in the control of hemopoietic differentiation. In that event they probably recognize a cell type associated with other than viral specificities.

IN VITRO CHARACTERISTICS OF MOUSE NK CELLS

It is now well established that in the mouse the NK cell is not a mature T cell (9, 10) as it lacks detectable amounts of theta-antigen and inasmuch as nude mice exhibit high activity. Furthermore, mouse NK cells lack surface immunoglobulin as well as C3 receptors (9, 10). Despite earlier negative findings (10), Herberman , (11) have concluded that NK cells have low but detectable amount of Fc receptors. There is general agreement that the NK cell is poorly adherent and nonphagocytic (3, 4, 9, 10). Accordingly, NK cells in mice are neither mature B nor T cells. Reports describing the rat NK cell seem to be in concurrence with those from mouse systems (12, 13). Here too, the killer cell seems to be of non-T origin as measured by a heterologous anti-T serum. Also, rat NK cells lack C3 and Fc receptors, and are poorly adherent and nonphagocytic.

Even this brief summary suffices to conclude that mouse and rat NK cells constitute a cell type clearly distinguishable from previously defined cytotoxic cells.

NONGENETIC FACTORS INFLUENCING NK ACTIVITY

NK activity in the mouse can be influenced by a number of factors as listed in Table 1.

TABLE 1

Influence of Nongenetic and Genetic Factors

First to be mentioned are some nongenetic methods used to manipulate NK activity. The pronounced influence on NK activity of the age of the animal is noteworthy. Fetal liver and spleen cells from new-born mice show little or no activity. In contrast to immune T cells, which in mice mature during the first week of life, the onset of NK activity does not occur until three weeks of age, and peak activity is seen in 6–8 week old mice. Thereafter there was a marked decline of activity, 6–12 months old mice showing very low activity (1, 2). In rats a roughly similar situation has been observed (12, 13).

There are several lines of evidence that NK cells are of major importance for rejection of subcutaneously injected tumor cells (14, 15). NK cells can probably migrate from the spleen or peripheral blood, organs known to contain the highest NK activity, into the local site of tumor growth. Alternatively, they could be recruited from cells already present in various organs. It will be important to ascertain the influence of tumor induction and of immunization with tumor cells on NK activity in peripheral lymphoid organs. Becker and Klein (6) have studied the NK activity in three separate models of tumor-bearing animals, and in all three systems a pronounced suppression of NK activity in the spleen was found.

Herberman (16) have determined the effect of host challenge on NK activity and found that in nude, as well as in normal mice of various ages, reactivity could be augmented by inoculation of tumor cells. This augmented cytotoxicity reached a peak three days after inoculation, and was only seen with tumor cells that bore target structures recognized by NK cells. The authors concluded that, in most respects, this augmentation of NK reactivity was consistent with the stimulation of specific memory cells by reexposure to antigen.

It has also been established by the same authors as well as by other groups that NK activity in mice could be augmented by other agents, notably allogenic cells, bacteria, and viruses. Wolfe and collaborators (17) demonstrated that viable BCG organisms given i.p. induced in the peritoneal cavity of normal mice a population of cytotoxic cells. These cells appeared within a few days after BCG administration, and had many features in common with NK cells. Also, i.p. administration by heat-killed elicited a similar phenomenon (Ojo , personal communication). Thus, augmented NK activity after administration of bacterial adjuvants or viruses show that NK cells can be boosted nonspecifically, but the mechanism responsible for this nonspecific boosting is not known.

GENETIC REGULATION OF NK ACTIVITY

Early in the course of the study of NK cells in mice, it was found in different laboratories that various mouse strains differed consistently in NK reactivity (1, 2). This pronounced strain difference is indicative of a genetic influence and was investigated by further genetic analyses. High reactivity appears to be dominant; when the low reactive A-strain was crossed with various other strains, and cells from these F1 hybrids tested for NK activity against semisyngeneic YAC lymphoma of A origin, reactivity resembled that of the high-reactive parent (18). This high NK activity in F1 mice has suggested a possible relationship between NK cells and the so-called “hybrid effect.” Since the time...