Colony-stimulating factors are glycoprotein molecules required, at least in vitro, for clonal proliferation and differentiation of myeloid precursors. These molecules are produced by a wide variety of cell types and are produced at dramatically augmented rates upon stimulation with antigenic or inflammatory substances. Recent evidence indicates that certain CSF may also influence functional activities of more mature cells including macrophages and is highly suggestive that at least macrophage-specific CSF can influence both accessory and possibly effector functions of these cells as well as acting as specific growth factors. The long term goal of this project is to define the role(s) of CSF in regulation of macrophage functions during inflammatory reactions and infectious diseases.
The specific aims i nclude the purification of cytokine, lymphokine and monokine macrophage-type CSF and the preparation of specific neutralizing antibody against each molecule. The purified CSF preparations will be compared for stimulation of both myeloproliferation and macrophage functional activities. Macrophage functional activities to be assessed include production of interleukin 1, Alpha + Beta types of interferon, E prostaglandins, superoxide ion and antigen processing and presentation. Additional experiments are designed to determine if CSF responsiveness is limited to phenotypic subclasses of more mature mononuclear phagocytes and if functional stimulation by CSF is a direct effect on the responding cell, mediated by accessory cells or part of a multiple signal sequence. Evidence also suggests that CSF may play an integral role in regulation of specific immune responses. Experiments are designed to determine if CSF influences both in vitro and in vivo induction and differentiation of antigen specific cytotoxic T lymphocytes. Specifically effects of both exogenous and endogenous CSF on the induction of type 1 Herpes Simplex virus specific cytotoxic T cells will be assessed and defined.
