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Doctoral thesis, 1997

The interferon-α/β system studied in vitro and in vivo

Eloranta, Maija-Leena;

Abstract

In this thesis the interferon-a/p (IFN-a/p) system was studied, especially the IFN-a/p producing cells (IPCs) in man and mouse. The phorbol 12-myristate 13-acetate (PMA) by activating proteinkinase C efficiently inhibited expression of IFN-a/p genes induced by Sendai virus in monocytes and by Herpes simplex virus (HSV) in the natural IPC (NIPC), the two major IPCs in human blood. A physiological mechanism controlling IFN-a/p production could be involved, perhaps relevant for the tumor promoting activity of PMA. Analysis of the phenotype of human NIPC, the most versatile and perhaps important IPC, was carried out by flow cytometry and sorting. These HSV-induced IPCs did not belong to the lymphoid or myeloid developmental lineages, but had characteristic light scatter. The further characterization of IPCs was done in the mouse. Because human NIPC might be immature dendritic cells (DCs), the IFN-a/p responses of two murine DC lines were studied. One of them responded to virus and bacteria in a NIPC-like fashion, and will become a useful experimental tool. Infrequent but efficient NIPC-like cells were also detected among normal cells derived from lymphoid organs of mice. When HSV was injected intravenously in mice, highly productive IPC were almost only found in the marginal zones of splenic white pulp. The IPCs had the cell adhesion molecule sialoadhesin and may be metallophilic macrophages, but not DCs or common macrophages. Subcutanous injection of HSV in mice resulted in appearance of IPCs mainly in the regional lymph node and especially in its subcapsular parts. A concomitant early lymph node swelling due to accumulation of lymphocytes was seen, in part dependent on produced IFN-a/p. Also in mice intracerebrally infected by lymphocytic choriomeningitis virus (LCMV), IPCs appeared in splenic marginal zones and in lymph nodes. No IFN-a and little IFN-p production was seen in the brain. This differential activity of the IFN-a/p system explains in part its pivotal effects on the course of LCMV infections.

Keywords

interferon-alpha; interferon-beta; dendritic cells; spleen; lymph node; Herpes simplex virus; Sendai virus; Lymphocytic choriomeningitis virus; phorbol ester

Published in

Acta Universitatis Agriculturae Sueciae. Veterinaria

1997, number: 15
ISBN: 91-576-5400-X
Publisher: Swedish University of Agricultural Sciences

Authors' information

Eloranta, Maija-Leena
Swedish University of Agricultural Sciences, Department of Veterinary Microbiology

UKÄ Subject classification

Pathobiology
Microbiology in the medical area

URI (permanent link to this page)

https://res.slu.se/id/publ/117379