Showing papers by "Emil R. Unanue published in 1984"

Alpha-fetoprotein inhibits macrophage expression of Ia antigens.

Abstract: Murine alpha-fetoprotein (AFP) is a major protein in amnionic fluid and perinatal sera. AFP has been postulated to contribute to the immunologic hyporesponsiveness of the fetus and neonate, as well as protecting the fetus from rejection by the mother. We now report that AFP acts in vitro to inhibit macrophage expression of cell surface Ia antigens, the class II glycoproteins of the major histocompatibility gene complex. In culture, macrophages incubated with a T cell lymphokine developed Ia as detected by either immunofluorescence or a cell radioimmunoassay. Both mouse amnionic fluid and AFP inhibited the expression of Ia in a dose-dependent manner. Five preparations of AFP derived from three sources--day-old neonates, amnionic fluid, and a hepatoma cell line--were effective. The concentration of AFP that inhibited by 50% the expression of Ia was about 10(-6) M. Mouse amnionic fluid and AFP did not affect the viability of the macrophage nor was the surface expression of H-2K and C3 receptors affected. The inhibitory effect of AFP did not depend on the presence of T cells in the culture. AFP did not appear to inhibit the direct interaction of lymphokine with macrophages; AFP did inhibit if given days after a pulse of lymphokine. The concentrations of prostaglandins carried by AFP were insignificant and could not explain the inhibitory effects.

Antigen processing and presentation by macrophages

Abstract: The classical macrophage is one of the most important cells involved in presenting antigen to helper T cells, because of its ability to regulate its expression of Ia molecules and to encounter and process particulate and soluble antigens. We have summarized in this report studies examining the handling by macrophages of two different antigens, the bacteria Listeria monocytogenes and the protein hen egg white lysozyme (HEL). The purpose was to identify potential sources of immunogenic peptides. Presentation of Listeria required an intracellular processing stage sensitive to lysosomotropic drugs. The Listeria required internalization and processing, after which immunogenic molecules were recognized by T cells on the macrophage surface. Metabolic studies showed that Listeria-derived peptides were released by macrophages that had phagocytosized the bacteria. The release of these peptides was a temperature-dependent process, unaffected by inhibiting lysosomal catabolism by treatment with chloroquine. Listeria-derived peptides were also detected on the surface of the macrophage. These peptides behaved like integral membrane proteins, some of which persisted for at least 24 hr at the macrophage surface. When tested for immunogenicity, the released peptides were very weakly immunogenic. The membrane-associated peptides alone could not stimulate Listeria-specific T cells, but could be reprocessed by additional macrophages and subsequently stimulate the T cells. A defined antigen system using HEL-specific T-cell hybridomas was used to examine the processing of HEL. Presentation of HEL required a chloroquine-sensitive intracellular processing stage. In examining two T-cell hybridomas, a differential requirement for antigen processing was determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Immune complexes suppress cellular immunity.

Abstract: Patients with AIDS exhibit a remarkable suppression of the immune response to viruses and certain intracellular pathogens.’-’ The immune response to these pathogens is thought to be based on activation of T cells of the helper phenotype (TH). Patients with AIDS have a relative deficit of TH cells compared to T cells of the suppressor phenotype (T,) cells. The relationship, however, between these findings and the lack of active immunity is not clear. In fact, a causal relationship between the decreased T,/T, ratio in these patients and the absence of effective immunity has not been established. The lack of T, cells could be the cause or the effect of the immunosuppression characterizing AIDS. Moreover, little work has been published on possible deficits in other parts of the immune system. In particular, the role of the macrophage and other antigen-presenting cells as both the inducers of TH cells and the recipients of TH-cell signals has received little attention. A detailed understanding of the pathophysiology of AIDS will depend on our knowledge of the mechanisms of antiviral and antibacterial immunity. Little is known in detail about the human immune response to intracellular pathogens. Animal models, however, are presently much better understood. This paper will deal with a murine model of infection with an intracellular pathogen, and a novel system that we have developed for suppressing resistance to this pathogen. We do not feel that this model is necessarily related to the cause or pathophysiology of AIDS. Rather it is a model that is amenable to experimental manipulations delineating mechanisms of immunosuppression. It is our hope that the experiments presented here will stimulate experiments in human systems that will serve to further define the immunodeficit(s) present in AIDS. In this paper we will first review what is known about the murine immune response to the facultative intracellular pathogen Listeriu monocytogenes. This relatively wellunderstood system has been extensively studied both in vitro and in vivo. We will then describe a mechanism for suppressing the immune response to Listeria. Lastly, we will discuss the possible implications of these studies for understanding the immune deficit in AIDS and immunosuppressed states in general. Most of the data presented in this paper has been published elsewhere.‘

Propagation of B lymphocytes in vitro.

Abstract: Several differentiative states of the mature B lymphocyte are well known, including clonal expansion, antibody secretion, heavy chain class switching, and somatic mutation. However, the precise sequence of these differentiative events, and the mechanism by which immunoregulatory cells and mediators influence this sequence remains uncertain. This is due in large part to the paucity of suitable clonal B cell lines which may be propagated while retaining differentiative potential (Howard, 1981; Sredni, 1981; Whitlock, 1982).