Macrophages and natural killer cells

This book is the outcome of a meeting held in Davos, Switzerland, February 7-12, 1982 focused primarily on mononuclear phagocytes and on natural killer (NK) cells. This IX International RES Congress was attended by 489 scientists from 31 countries and there were 340 scientific presentations in oral or poster session. The essential purpose of the Congress was to bring together scientists representing various aspects of mononuclear phagocyte biology to review and examine critically the effects and mechanisms of macrophage growth control as well as the participation of these cells in the afferent and efferent limbs of the immune response. Additional topics included the production and distribution of mononuclear phagocytes; the intrinsic and extrinsic regulation of these cells; and the origin, nature, function and regulation of NK cells. The ultimate goal of the Congress was to enhance communication between scientists in various countries and disciplines so that new research directives could be defined with which to explore basic aspects of macrophage and NK cell participation in the control of cancer and infection. The macrophage is receiving increased scientific attention which is a proper reflection of the central role this cell plays in homeostasis. The Congress was designed to emphasize the following unique and timely aspects of macrophage biology: (a) the various growth regulating aspects of macrophages were examined with respect to both normal and abnormal cellular proliferation. Discussion focused upon the regulatory role of macrophages in hematopoiesis and lymphocytic and fibroblastic proliferation as examples of normal cell processes, and these effects were contrasted with those on neoplastic and transformed cells. (b) Regulation of macrophage function by prostaglandins, complement, and interferon was analyzed from the point of view of an auto-regulatory network. (c) The parallel between chemotaxis and phagocytosis was explored with reference to recognition events and cytoskeletal function. (d) The role of macrophages in the afferent and efferent limbs of the immune response focused on the nature of lymphocyte-macrophage communication and the role of I region associated determinants. This focus on macrophages and homeostasis generated certain questions which formed the basis of the Congress and which are addressed in the papers collected in this volume. Among the questions are the following: By what means does the macrophage plasma membrane recognize foreigness? Is chemotaxis a form of directional phagocytosis? How are trans-membrane signals utilized to effect microfilament and microtubular functions essential to chemotaxis and phagocytosis? Can monoclonal antibodies or physical properties be used to define or isolate subsets of macrophages with restricted activities? Do all macrophages have the capacity to express Ia antigens despite the fact that only a minority of the cells express the product of the Ir gene at any given time? How do lymphokines activate macrophages? Is a cell which produces colony stimulating factor capable of responding to lymphokine and becoming cytotoxic to tumor cells? Do monokines and NK cells act as suppressor cells to certain lymphocyte functions? Are the prostaglandins and colony stimulating factors that participate in hematopoiesis also stimulating or retarding growth of transformed cells? It is becoming increasingly evident that NK cells and macrophages share the common property of non-specific cytotoxic and bactericidal activities. Although the spectrum of susceptible target cells may differ and the two cells may be derived from different cell lineages, it appeared appropriate to include in the Congress and in this volume a discussion of natural resistance mechanisms. Spontaneously occurring cytotoxic cells may influence cancer emergence and hematopoietic differentiation as well as graft rejection and viral infection. The activity of these cells is modulated by interferon and other agents which also activate macrophages. In the discussion oriented symposium which concluded the Congress and which is reproduced here, the critical issues were addressed of whether or not the cells responsible for natural resistance to grafts of renal, hematopoietic and leukemic cells, to carcinoma, sarcoma and melanoma cells and to certain viruses are related and which kinds of molecules are recognized on the surface of neoplastic and non-neoplastic targets. In addition, the nature of surface markers on effectors cells and the regulation of natural resistance mechanisms were presented, including the interaction of effector and regulatory accessory cells.