THE ROLE OF T-CELL SUBSETS AND CYTOKINES IN THE REGULATION OF INTRACELLULAR BACTERIAL-INFECTION

Cellular immune responses are a critical part of the host's defense ag ainst intracellular bacterial infections. Immunity to Brucella abortus crucially depends on antigen-specific T cell-mediated activation of m acrophages, which are the major effecters of cell-mediated killing of this organism. T lymphocytes that proliferate in response to B. abortu s were characterized for phenotype and cytokine activity. Human, murin e, and bovine T lymphocytes exhibited a type 1 cytokine profile, sugge sting an analogous immune response in these different hosts. In vivo p rotection afforded by a particular cell type is dependent on the antig en presented and the mechanism of antigen presentation. Studies using MHC class I and class II knockout mice infected with B. abortus have d emonstrated that protective immunity to brucellosis is especially depe ndent on CD8+ T cells. To target MHC class I presentation we transfect ed ex vivo a murine macrophage cell line with B. abortus genes and ado ptively transferred them to BALB/c mice. These transgenic macrophage c lones induced partial protection in mice against experimental brucello sis. Knowing the cells required for protection, vaccines can be design ed to activate the protective T cell subset. Lastly, as a new strategy for priming a specific class I-restricted T cell response in vivo, we used genetic immunization by particle bombardment-mediated gene trans fer.