Forschungs- & Entwicklungsinformationsdienst der Gemeinschaft - CORDIS

FP5

FMD TROPISM Berichtzusammenfassung

Project ID: QLK2-CT-2002-01719
Gefördert unter: FP5-LIFE QUALITY
Land: Switzerland

Importance of FMDV interaction with dendritic cells (myeloid DC and plasmacytoid DC - natural interferon-producing cells) for efficient induction

Background: Dendritic cells (DC) play a central role in immune response development and are an important target for vaccines. These cells are critical for initiating and controlling both innate and adaptive (specific) immune responses. In this sense, efficacious vaccines must efficiently interact with the DC, leading to the correct processing of the vaccine antigen by the DC. Only then will an efficient stimulation of the appropriate immune defence development occur. It is therefore important to consider the manner by which FMDV interacts with DC, and the particular efficiency when heparan sulphate (HS) binding capacity is present. To this end, it is important to understand the immunological consequences of infection of DC with HS- and non-HS-variant viruses. Accordingly, the aim was to determine the immunological consequences of FMDV interaction with monocytic cells.

- FMDV interaction with myeloid DC
FMDV antigen-positive DC clearly process the virus antigen, being efficient at inducing antigen specific responses by T lymphocytes isolated from immune animals. Moreover, antigen-specific B lymphocytes were also induced by FMDV-carrying DC to produce specific antibody this was dependent on the presence of DC carrying FMDV antigen. The additional presence of the CD6+ T cells augmented the responsiveness of the B lymphocytes, but this could be replaced by IL-2 plus IL-4.
DC, which had endocytosed-non-HS virus, would also induce antigen-specific T and B cell activities, showing that antigen had indeed been internalised and was probably processed too rapidly to be visualised. Nevertheless, the efficiency of inducing T and B cell activities was higher with the HS-binding virus, reflecting the greater retention of this type of antigen in the DC. That is, the DC are showing evidence for a more efficient uptake and retention of HS-binding virus (as found in vaccine preparations) for processing and presentation to the T and B lymphocytes. This was observed with both live and inactivated virus. Consequently, the presence of the FMDV in DC does not impair their ability to induce T and B lymphocyte activity. On the contrary, efficient uptake and retention of the virus by DC is essential.

- FMDV interaction with plasmacytoid DC (natural interferon-producing cells)
FMDV (live or inactivated) did not induce IFNa production by the natural interferon-producing cells (NIPC), nor did it interfere with the capacity of known stimuli of NIPC to induce interferon production. Interestingly, when live FMDV was complexed with immune IgG, there was a clear ability to induce interferon production by NIPC.

This was dependent on the internalised virus producing a dsRNA intermediate, although the replicative cycle was abortive.

This is important for understanding the importance of these innate defenders during the development of specific immunity, and would clearly present a critical defence at times when antibody development was only beginning. That is, the roles played by NIPC is of particular relevance early post-vaccination, and would be of high value under conditions of emergency vaccination when rapid protection is required. The NIPC would respond to immune complexes, even when the virus infectivity was not neutralised. The production of the interferon would enhance the immune responses, but also assist the anti-viral defence, aiding the host to resist the virus infection until such times as the antibody levels became fully protective. This could explain the means by which vaccinates can be protected early post-vaccination when antibody levels are still low.

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