Holmgren. 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 7-expressing memory T cells produced around 10-fold more IFN- than the remaining populations. In conclusion, we demonstrate that oral vaccination with a CCT020312 live oral bacterial vaccine induces antigen-specific CD4+ and CD8+ memory T cells, almost all of which express the gut-homing integrin 7. Although the kinetics and homing characteristics of B-cell responses in humans after mucosal immunizations have been extensively studied, mucosal T-cell responses after oral vaccination have been investigated in only a few studies (9, 19, 22, 23, 24). Oral vaccination with the attenuated serovar Typhi strains Ty21a (Vivotif) and CVD908 has been shown to induce proliferative responses, production of gamma interferon (IFN-), and antibody-dependent antibacterial activity by peripheral blood lymphocytes in the majority of vaccinated subjects at 3 weeks postvaccination (19, 21). Furthermore, a more recent report exhibited that volunteers vaccinated with two doses of the CVD908 strain developed CD8+ cytotoxic-T-lymphocyte precursors, which after a short in vitro expansion were capable of killing serovar Typhi-infected cells (18). Except in that study, the relative contributions of CD4+ and CD8+ T cells in the response to oral vaccinations have not been investigated and the kinetics and homing patterns of the T-cell responses have not been evaluated in any detail. A central event in the homing of lymphocytes to CCT020312 different tissues is the adhesion of lymphocytes by means of surface-homing receptors to binding structures, so-called addressins, on endothelial cells. Because some of the addressins are distributed in a tissue-restricted manner, tissue-specific homing of cells to corresponding homing receptors can occur. Some of the homing receptors that have been identified are 47, which guides cells to the mucosal lamina propria (17); l-selectin, which guides cells to peripheral lymph nodes (6); and cutaneous lymphocyte antigen, which guides cells to the skin NOS3 (1). The aim of this study was to determine the kinetics of circulating, mucosa-derived CD4+- and CD8+-T-cell responses after oral vaccination as well as the expression of intestinal homing receptors on T cells activated by the vaccine. As a model vaccine, we chose the live, attenuated serovar Typhi vaccine Ty21a, which previously has been shown to induce reliable antibody responses in intestinal secretions as well as circulating, vaccine-specific B cells and T cells (11, 12, 20, 21, 23). METHODS and Components Topics and vaccinations. Eight healthful adult people, six ladies and two males (26 to 53 years; median age group, 37), without the past background of serovar Typhi disease or vaccination against typhoid fever, volunteered to take part in the scholarly research. The volunteers received an dental capsule including 2 109 to 5 109 live serovar Typhi Ty21a bacterias (Vivotif) on times 0, 2, and 4. Fifty milliliters of heparinized bloodstream was gathered from each volunteer prior to the 1st vaccination on day time 0 and on times 7, 14, and 21. Bloodstream examples had been gathered through the 1st two volunteers on times 3 also, 29, and 35. The scholarly study was approved by CCT020312 the Ethical Committee for Human being Study at G?teborg College or university, and informed consent was from each volunteer before involvement. Cell planning. Peripheral bloodstream mononuclear cells (PBMC) had been isolated by denseness gradient centrifugation on Ficoll-Paque (Pharmacia, Uppsala, Sweden). The cells had been washed 3 x with phosphate-buffered saline (PBS) and resuspended.
