In Vivo Compartmentalization of Functionally Distinct, Rapidly Responsive Antigen-Specific T-Cell Populations in DNA-Immunized orSalmonella entericaSerovar Typhimurium-Infected Mice

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Abstract
The location and functional properties of antigen-specific memory T-cell populations in lymphoid and nonlymphoid compartments following DNA immunization or infection withSalmonellawere 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-γ)-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 ofSalmonella entericaserovar Typhimurium was also quantitated by an ex vivo restimulation with bacterial lysate to detect the totalSalmonella-specific memory pool. Mice immunized up to 6 months previously withS. entericaserovar Typhimurium had bacterium-specific CD4+T cells that were capable of producing IFN-γ or tumor necrosis factor alpha (TNF-α) at each site analyzed. Similar findings were observed for CD8+T cells that were capable of producing IFN-γ, while a much lower frequency and more restricted distribution were associated with TNF-α-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 sameSalmonella-infected individuals and demonstrates the organ-specific functional compartmentalization of memory T cells afterSalmonellainfection.