BRUCELLA-ABORTUS INDUCES A NOVEL CYTOKINE GENE-EXPRESSION PATTERN CHARACTERIZED BY ELEVATED IL-10 AND IFN-GAMMA IN CD4-CELLS( T)

Immunization of BALB/c mice with killed Brucella abortus (BA) has prev iously been shown to increase serum IgG2a levels and long-term T cell clones from these mice secrete T(h)1-associated cytokines: IFN-gamma a nd IL-2 but not IL-4 or IL-5. We analyzed cytokine gene expression fol lowing primary immunization with BA to determine when CD4+ T cells fir st express cytokine genes and whether specific hypothesized cytokine p atterns (e.g. T(h) precursor, T(h)0) could be identified prior to a T( h)1-like pattern. Our results demonstrated a highly consistent and nov el pattern of T(h)1/T(h)2 cytokine gene expression characterized by el evated IL-10 and IFN-gamma in CD4+ T cells which rapidly manifests its elf and is sustained for at least 10 days after immunization. No eleva tion in IL-2 cytokine gene expression was observed and treatment of BA -immunized mice with blocking anti-IL-2 antibodies had no effect on th e cytokine gene expression pattern, although treatment with anti-IFN a ntibodies resulted in increased IL-4, IL-5, and IL-9 cytokine gene exp ression, in the absence of any change in IFN-gamma or IL-10 as early a s 4 days after immunization. These results suggest that a whole pathog en may trigger sufficient costimulatory signals to rapidly induce effe ctor T cells in the absence of elevated IL-2 and that IL-10 is specifi cally elevated in certain T(h)1-like responses.