Brucella abortus induces a novel cytokine gene expression pattern characterized by elevated IL-10 and IFN-gamma in CD4+ T cells.
Immunization of BALB/c mice with killed Brucella abortus (BA) has previously been shown to increase serum IgG2a levels and long-term T cell clones from these mice secrete Th1-associated cytokines: IFN-gamma 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 Th1/Th2 cytokine gene expression characterized by elevated IL-10 and IFN-gamma 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-immunized 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 cytokine gene expression, in the absence of any change in IFN-gamma 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.
Svetić
A
A
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Jian
Y C
YC
Lu
P
P
Finkelman
F D
FD
Gause
W C
WC
D000818:Animals; D002003:Brucella abortus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics*; D007376:Interleukin-2 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism
D007376:Interleukin-2; D016753:Interleukin-10; D007371:Interferon-gamma