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Infection and Immunity, November 2004, p. 6390-6400, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6390-6400.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

In Vivo Compartmentalization of Functionally Distinct, Rapidly Responsive Antigen-Specific T-Cell Populations in DNA-Immunized or Salmonella enterica Serovar Typhimurium-Infected Mice

Alun C. Kirby,1,{dagger} Malin Sundquist,2 and Mary Jo Wick1,2*

Department of Cell and Molecular Biology, Section for Immunology, Lund University, Lund,1 Department of Clinical Immunology, Göteborg University, Göteborg, Sweden2

Received 26 August 2003/ Returned for modification 24 October 2003/ Accepted 26 July 2004

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.

* Corresponding author. Present address: Department of Clinical Immunology, Göteborg University, Guldhedsgatan 10, SE 413 46 Göteborg, Sweden. Phone: 46 31 342 4602. Fax: 46 31 342 4621. E-mail: mary-jo.wick{at}immuno.gu.se.

Editor: S. H. E. Kaufmann

{dagger} Present address: Department of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, United Kingdom.

Infection and Immunity, November 2004, p. 6390-6400, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6390-6400.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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