BRUCELLA-ABORTUS STIMULATES HUMAN T-CELLS FROM UNINFECTED AND HIV-INFECTED INDIVIDUALS TO SECRETE IFN-GAMMA - IMPLICATIONS FOR USE OF BRUCELLA-ABORTUS AS A CARRIER IN DEVELOPMENT OF HUMAN VACCINES

Brucella abortus has been characterized as a T-independent type 1 antigen/carrier in human and murine antibody responses. In this report it is shown that BA can activate human CD3+ T cells to secrete interferon-gamma (IFN-gamma). Unlike mitogens, such as phytohemagglutinin, this stimulation was associated with minimal T-cell proliferation or upregulation of interleukin-2 (IL-2) receptor. Monocytes inhibited BA-mediated IFN-gamma secretion since their removal resulted in increased responses, whereas adding monocytes back to cultures caused inhibition. BA elicited IFN-gamma from CD4+ and CD8+ T cells, although CD4+ T cells secrete significantly more (p < 0.05) IFN-gamma than CD8+ T cells. The ability of BA to elicit IFN-gamma from human T cells was inhibited in the presence of anti-Tac, suggesting that BA also induces IL-2 secretion and that IL-2 is involved in BA-mediated IFN-gamma secretion. Detectable IL-2 secretion was induced by BA in the presence of anti-Tac. Exogenous IL-2 acted synergistically with BA to enhance IFN-gamma secretion, suggesting that the amount of IL-2 released by BA alone was insufficient for optimal IFN-gamma release. Furthermore, addition of IL-2 to T cells from individuals with poor or absent responses to BA, including individuals infected with HIV-1, restored their ability to secrete IFN-gamma in response to BA. These data indicate that BA is capable not only of activating human B cells but can also induce T cells, probably of the TH1 phenotype, to secrete IFN-gamma. Production of IFN-gamma in response to BA has implications in the proposed development of BA as a carrier for human vaccines, since IFN-gamma has multiple effects including macrophage activation, B-cell differentiation, and antiviral activity.