CYTOKINES AND ANTI-CYTOKINE AUTOANTIBODIES DURING EXPERIMENTAL AFRICAN TRYPANOSOMIASIS IN MICE WITH DISRUPTED INTERFERON-GAMMA AND INTERFERON-GAMMA RECEPTOR GENES

We studied cytokines and anti-cytokine autoantibodies (Aabs) during T. b.brucei infections in IFN-gamma(-/-), IFN-gamma R-/- and wild-type mi ce. Increased serum levels of IFN-gamma, TNF-alpha and IL-4 with decre ased Aabs to these cytokines were recorded early during infections in all mice (except IFN-gamma in IFN-gamma(-/-) mice). Later, these respo nses were reversed, and surprisingly Aabs reacting to IFN-gamma in the IFN-gamma(-/-) mice were detected. To examine the possibility that an IFN-gamma immunoreactive molecule might be expressed due to infection s and upon gene deletion, anti-IFN-gamma antibody was inoculated and r esulted in abrogation of such Aabs. The scenario was different for IL- 10 and TGF-beta since IFN-gamma R-/- and wild-type mice showed low cyt okines and high Aabs early during infections, but later high cytokines and low Aabs were registered. Interestingly, IFN-gamma(-/-) mice exhi bited reversed levels of both IL-10 and TGF-R, and also of their Aabs. Fab fragments of purified serum immunoglobulins showed binding and ne utralizing effects in biological assays. Pre-absorption of the Fab fra gments with a cytokine inhibited the binding and neutralization effect s of this cytokine, but not of other cytokines. These results highligh t an important role for autoimmunity in cytokine regulation, and that genomic deletion of IFN-gamma modulates cytokines and their Aab respon ses in experimental African trypanosomiasis.