Phagocytosis-inducing factor (PIF) is a newly described human lymphokine which we have recently described, partially purified, and shown to be distinct from interferon-gamma and other lymphokines. PIF is defined biologically by stimulation of phagocytosis by cells of the human monocytoid line, U937. Preliminary data suggest that PIF may be a differentiation- inducing factor for U937 cells and possibly other cells and that PIF may play an important role in the regulation of immunological interactions between T lymphocytes and mononuclear phagocytes. Our ultimate goal is to determine the importance of PIF in the pathogenesis of diseases characterized by deficient or excessive immune functioning, such as AIDS or autoimmune disease, and the potential usefulness of PIF int he treatment of such diseases. The goal of the present proposal is to determine the biochemical characteristics, molecular actions, and immunologic functions of PIF. This goal will be accomplished in four subprojects. In the first project, we will utilize a specialized cell culture system, along with well-established methods for protein purification, to biochemically purify PIF, which is produced constitutively by certain T cell lines we have identified. The second project will be to prepare monoclonal antibodies specific for PIF and use these for affinity-purification of PIF and development of a specific immunoassay for PIF, according to well-established procedures. We will then delineate the molecular characteristics of PIF, including molecular weight, isoelectric point, and degree and functional importance of glycosylation. In the third project we will use purified PIF and monoclonal antibodies to PIF to define the effects of PIF on cell so the immune system and cells from subjects infected with human immunodeficiency virus, in particular testing the hypotheses that PIF is an amplifier of antigen-induced reactions and that PIF potentiates T cell activation and susceptibility of T cells to infection with the human retroviruses HTLV-I and HIV; and 3) to develop a solid- phase immunoassay for PIF. In the final stage, we will use this immunoassay to characterized the subset of T4 positive lymphocytes that produces PIF and to determine its relationship of this subset to the subsets of T4 positive cells that 1) proliferate in response to soluble antigen and 2) can be transformed with HTLV-I. These studies will provide a rational basis for determining if PIF, or neutralizing antibodies to it, may be potentially useful in the treatment of diseases of deficient immune function.
| Carini, C; Margolick, J; Yodoi, J et al. (1988) Formation of IgE-binding factors by T cells of patients infected with human immunodeficiency virus type 1. Proc Natl Acad Sci U S A 85:9214-8 |
