AN ANALYSIS, USING MONOCLONAL-ANTIBODIES, OF THE ROLE OF INTERFERON-GAMMA IN OVINE IMMUNE-RESPONSES

A mAb (IFN-9) which neutralizes biologically active ovine and bovine IFN-gamma was used to deplete levels of the cytokine in vivo in sheep and examine the consequences for immune responses to adjuvanted antigen and skin reactivity to Bacillus-Calmette-Guerin (BCG). Groups of sheep were immunized with ovalbumin in the adjuvants, Quil A or dextran sulphate (MW 500 000; DXS), both of which elicit production of IFN-gamma. MAb anti-IFN-gamma or an isotype control mAb (anti-carbonic anhydrase positive particles) were inoculated i.v. during primary and/or secondary responses. Reactions monitored in efferent prefemoral lymph indicated that anti-IFN-gamma effectively depleted levels of IFN-gamma in lymph but had no effects on the magnitude and kinetics of lymphocyte and lymphoblast traffic, or total or isotypic titres of specific Ig. When incubated in vitro with ovalbumin, antigen-reactive cells from anti-IFN-gamma treated sheep did not produce IFN-gamma, suggesting an on-going modification to cytokine production. In contrast, skin reactions to purified-protein derivative in sheep immunized with BCG were reduced by < 40% by anti-IFN-gamma. The results indicate that IFN-gamma production may not be obligatory for delayed-type hypersensitivity reactions or for the adjuvant action of Quil A or DXS, and that specific mAb can alter the profile of cytokines produced by antigen-reactive cells in sheep.