Brucella abortus induces a novel cytokine gene expression pattern characterized by elevated IL-10 and IFN-γ in CD4+ T cells

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Abstract
Immunization of BALB/c mice with killed Brucella abortus (BA) has previously been shown to Increase serum lgG2a levels and long-term T cell clones from these mice secrete Th1-associated cytokines: IFN-γ and IL-2 but not IL-4 or IL-5. We analyzed cytokine gene expression following primary immunization with BA to determine when CD4+ T cells first express cytokine genes and whether specific hypothesized cytokine patterns (e.g. Th precursor, Th0) could be identified prior to a Th1-like pattern. Our results demonstrated a highly consistent and novel pattern of Th 1/Th2 cytokine gene expression characterized by elevated IL-10 and IFN-γ in CD4+ T cells which rapidly manifests itself and is sustained for at least 10 days after immunization. No elevation in IL-2 cytokine gene expression was observed and treatment of BA-immunlzed mice with blocking anti- IL-2 antibodies had no effect on the cytokine gene expression pattern, although treatment with anti-IFN antibodies resulted in increased IL-4, IL-5, and IL-9 cytoklne gene expression, In the absence of any change In IFN-γ or IL-10 as early as 4 days after immunization. These results suggest that a whole pathogen may trigger sufficient costimulatory signals to rapidly induce effector T cells in the absence of elevated IL-2 and that IL-10 Is specifically elevated in certain Th1-like responses.

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