ABSTRACT
EXPERIMENTAL AUTOIMMUNE DISEASE Alfons Billiau, H.Heremans and P.Matthys
Rega Institute, University of Leuven, Leuven (Belgium)
The lymphokine interferon-γ (IFN-γ) affects autoimmune diseases in many ways, as it targets antigen-presenting cells, lymphokineproducing T cells, cytotoxic T cells, antibody-producing B cells and endothelial cells, each of which have a role to play in the initiation and progression of auto-immune disease. In experimental models, exogenous as well as endogenous IFN-γ have invariably been found to dramatically affect disease severity, in some models in a positive, in others in a negative direction and in still others in either direction depending on time and circumstances. A system of rules allowing to accommodate and eventually to predict these various effects is only slowly emerging In particular, the role currently assigned to IFN-γ by the Th1/Th2 paradigm has proven to be insuffciently detailed for the paradigm to be reliable as a framework for setting the rules. IFN-γ, induced in the target organ by an exogenous agent, can potentiate initial tissue damage and autoantigen presentation and may thus critically contribute to abrogation of peripheral tolerance. Disease models in which autoantibody formation is central; indicate that IFN-γ is crucial for T-B cell interaction to be adequate for the generation of antibodies against low-affinity autoantigens. In some models IFN-γ exerts an overall protective effect, emphasizing the ability of IFN-γ to install T-cell suppressive circuits. Finally, full understanding of the role of IFN-γ seems to require more detailed insight into emerging pathways such as the action via induction of chemokines.
