Role of T cells in innate and adaptive immunity against Murine Burkholderia pseudomallei infection
Van Rooijen, Nico
Titball, Richard W.
Bancroft, Gregory J.
University of Exeter (at the time of publication Richard Titball was at the Defence, Science and Technology Laboratory, Salisbury, UK); London School of Hygiene and Tropical Medicine; National Institute for Medical Research, Mill Hill, London; Vrije Universiteit, Amsterdam; Khon Kaen University, Khon Kaen, Thailand
The Journal of Infectious Diseases
Published by University of Chicago Press for the Infectious Diseases Society of America
Antigen-specific T cells are important sources of interferon (IFN)–γ for acquired immunity to intracellular pathogens, but they can also produce IFN-γ directly via a “bystander” activation pathway in response to proinflammatory cytokines. We investigated the in vivo role of cytokine- versus antigen-mediated T cell activation in resistance to the pathogenic bacterium Burkholderia pseudomallei. IFN-γ, interleukin (IL)–12, and IL-18 were essential for initial bacterial control in infected mice. B. pseudomallei infection rapidly generated a potent IFN-γ response from natural killer (NK) cells, NK T cells, conventional T cells, and other cell types within 16 h after infection, in an IL-12– and IL-18–dependent manner. However, early T cell– and NK cell–derived IFN-γ responses were functionally redundant in cell depletion studies, with IFN-γ produced by other cell types, such as major histocompatibility complex class IIint F4/80+ macrophages being sufficient for initial resistance. In contrast, B. pseudomallei–specific CD4+ T cells played an important role during the later stage of infection. Thus, the T cell response to primary B. pseudomallei infection is biphasic, an early cytokine-induced phase in which T cells appear to be functionally redundant for initial bacterial clearance, followed by a later antigen-induced phase in which B. pseudomallei–specific T cells, in particular CD4+ T cells, are important for host resistance.
© 2005 by the Infectious Diseases Society of America. All rights reserved.
193 (3), pp. 370-379