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Infection and Immunity, October 2002, p. 5622-5627, Vol. 70, No. 10
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.10.5622-5627.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Oral Immunization with a Salmonella enterica Serovar Typhi Vaccine Induces Specific Circulating Mucosa-Homing CD4⁺ and CD8⁺ T Cells in Humans

Department of Medical Microbiology and Immunology and Göteborg University Vaccine Research Institute, Göteborg University, 40530 Göteborg, Sweden

Received 22 February 2002/ Returned for modification 9 May 2002/ Accepted 19 June 2002

The kinetics and homing characteristics of T-cell responses in humans after mucosal immunizations have not been well characterized. Therefore, we have investigated the magnitude and duration of such responses as well as the homing receptor expression of antigen-specific peripheral blood T cells by using an oral model vaccine, i.e., the live, attenuated Salmonella enterica serovar Typhi vaccine (Ty21a). Eight volunteers were each given three doses of the vaccine 2 days apart, and blood samples, from which CD4⁺ and CD8⁺ T cells were selected by the use of magnetic beads, were collected before vaccination and at regular intervals thereafter. To purify the potentially antigen-specific gut-homing T cells, CD45RA^- integrin ß₇⁺ cells were further sorted by flow cytometry. The sorted cells were then stimulated in vitro with the serovar Typhi vaccine strain, and the proliferation of cells and the cytokine production were measured. Following vaccination, there was a large increase in both the proliferation of and the gamma interferon (IFN-) production by blood T cells stimulated with the vaccine strain. The responses were seen among both CD4⁺ and CD8⁺ T cells, although the CD8⁺ cells produced the largest amounts of IFN-. Peak responses were seen 7 to 14 days after the onset of vaccination. Furthermore, most of the IFN- produced by both CD4⁺ and CD8⁺ cells emanated from cells with the potential to home to mucosal tissues, as the integrin ß₇-expressing memory T cells produced around 10-fold more IFN- than the remaining populations. In conclusion, we demonstrate that oral vaccination with a live oral bacterial vaccine induces antigen-specific CD4⁺ and CD8⁺ memory T cells, almost all of which express the gut-homing integrin ß₇.

Editor: R. N. Moore

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