The role of T cell subsets and cytokines in the regulation of intracellular bacterial infection

Abstract

Cellular immune responses are a critical part of the hosts defense against intracellular bacterial infections. Immunity to Brucella abortus crucially depends on antigen-specific T cell-mediated activation of macrophages, which are the major effectors of cell-mediated killing of this organism. T lymphocytes that proliferate in response to B. abortus were characterized for phenotype and cytokine activity. Human, murine, and bovine T lymphocytes exhibited a type 1 cytokine profile, suggesting an analogous immune response in these different hosts. In vivo protection afforded by a particular cell type is dependent on the antigen presented and the mechanism of antigen presentation. Studies using MHC class I and class II knockout mice infected with B. abortus have demonstrated that protective immunity to brucellosis is especially dependent on CD8+ T cells. To target MHC class I presentation we transfected ex vivo a murine macrophage cell line with B. abortus genes and adoptively transferred them to BALB/c mice. These transgenic macrophage clones induced partial protection in mice against experimental brucellosis. Knowing the cells required for protection, vaccines can be designed 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 transfer.Correspondence

Induction of a Th1-type of immune response but not protective immunity by intramuscular DNA immunisation with Brucella abortus GroEL heat-shock gene

“…The two main features are, ®rst, the production of interferon (IFN)-ã by a CD4 Th1 subset that up-regulates the macrophage anti-Brucella activity and, second, the development of CD8 T lymphocytes that are able to lyse Brucella -infected cells [8,9]. DNA vaccines seem to offer the best approach to activate both cellular components of the immune system [10,11].…”

Interleukin-1 Receptor-Associated Kinase 4 Is Essential for Initial Host Control of Brucella abortus Infection

“…However, macrophages are considered the main cells of Brucella residence in the host (3). The immune response against Brucella infection involves many molecules and cells to trigger a Th1 immune response and activation of CD8 ϩ T cells (12,26,27). Furthermore, gamma interferon (IFN-␥) is essential for host control of Brucella infection (24,32,41).…”

A DNA Vaccine Encoding Cu,Zn Superoxide Dismutase of Brucella abortus Induces Protective Immunity in BALB/c Mice

“…Like other facultative intracellular bacterial pathogens, resistance to B. abortus depends on acquired cell-mediated immunity (CMI) (33). The development of Th1 subset CD4 ϩ lymphocytes that secrete gamma interferon (IFN-␥), a crucial cytokine that up-regulates the macrophage anti-Brucella activity, and the development of CD8 ϩ T lymphocytes that are able to lyse Brucella-infected cells (20,22) are the two main components of the protective response. Live, attenuated vaccines that can stimulate strong CMI responses are usually very effective against brucellosis.…”