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Search: WFRF:(Wick C) > (2002-2004)

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  • Kirby, Alun C, et al. (author)
  • In vivo compartmentalization of functionally distinct, rapidly responsive antigen-specific T-cell populations in DNA-immunized or Salmonella enterica serovar Typhimurium-infected mice.
  • 2004
  • In: Infection and immunity. - 0019-9567 .- 1098-5522. ; 72:11, s. 6390-400
  • Journal article (peer-reviewed)abstract
    • The location and functional properties of antigen-specific memory T-cell populations in lymphoid and nonlymphoid compartments following DNA immunization or infection with Salmonella were investigated. Epitope-specific CD8+ -T-cell expansion and retention during the memory phase were analyzed for DNA-immunized mice by use of a 5-h peptide restimulation assay. These data revealed that epitope-specific gamma interferon (IFN-gamma)-positive CD8+ T cells occur at higher frequencies in the spleen, liver, and blood than in draining or peripheral lymph nodes during the expansion phase. Moreover, this distribution is maintained into long-term memory. The location and function of both CD4+ and CD8+ Salmonella-specific memory T cells in mice who were given a single dose of Salmonella enterica serovar Typhimurium was also quantitated by an ex vivo restimulation with bacterial lysate to detect the total Salmonella-specific memory pool. Mice immunized up to 6 months previously with S. enterica serovar Typhimurium had bacterium-specific CD4+ T cells that were capable of producing IFN-gamma or tumor necrosis factor alpha (TNF-alpha) at each site analyzed. Similar findings were observed for CD8+ T cells that were capable of producing IFN-gamma, while a much lower frequency and more restricted distribution were associated with TNF-alpha-producing CD8+ T cells. This study is the first to assess the frequencies, locations, and functions of both CD4+ and CD8+ memory T-cell populations in the same Salmonella-infected individuals and demonstrates the organ-specific functional compartmentalization of memory T cells after Salmonella infection.
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3.
  • Kirby, Alun C, et al. (author)
  • The innate immune response differs in primary and secondary salmonella infection.
  • 2002
  • In: Journal of Immunology. - 1550-6606. ; 169:8, s. 4450-4459
  • Journal article (peer-reviewed)abstract
    • This study examines innate immunity to oral Salmonella during primary infection and after secondary challenge of immune mice. Splenic NK and NKT cells plummeted early after primary infection, while neutrophils and macrophages (M{phi}) increased 10- and 3-fold, respectively. In contrast, immune animals had only a modest reduction in NK cells, no loss of NKT cells, and a slight increase in phagocytes following secondary challenge. During primary infection, the dominant sources of IFN-{gamma} were, unexpectedly, neutrophils and M{phi}, the former having intracellular stores of IFN-{gamma} that were released during infection. IFN-{gamma}-producing phagocytes greatly outnumbered IFN-{gamma}-producing NK cells, NKT cells, and T cells during the primary response. TNF-{alpha} production was also dominated by neutrophils and M{phi}, which vastly outnumbered NKT cells producing this cytokine. Neither T cells nor NK cells produced TNF-{alpha} early during primary infection. The TNF-{alpha} response was reduced in a secondary response, but remained dominated by neutrophils and M{phi}. Moreover, no significant IFN-{gamma} production by M{phi} was associated with the secondary response. Indeed, only NK1.1+ cells and T cells produced IFN-{gamma} in these mice. These studies provide a coherent view of innate immunity to oral Salmonella infection, reveal novel sources of IFN-{gamma}, and demonstrate that immune status influences the nature of the innate response.
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  • Result 1-4 of 4

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