Immunization of Volunteers with Salmonella enterica Serovar Typhi Strain Ty21a Elicits the Oligoclonal Expansion of CD8+ T Cells with Predominant V{szligbeta} Repertoires

CD8+ T cells are likely to play an important role in host defense against Salmonella enterica serovar Typhi by several effector mechanisms, including lysis of infected cells (cytotoxicity) and gamma interferon (IFN-γ) secretion. In an effort to better understand these responses, we studied the T-cell receptor (TCR) repertoire of serovar Typhi-specific CD8+ T cells in humans. To this end, we determined the TCR beta chain (V{szligbeta}) usage of CD8+ T cells from three volunteers orally immunized with Ty21a typhoid vaccine by flow cytometry using a panel of monoclonal antibodies. Although TCR V{szligbeta} usage varied among volunteers, we identified oligoclonal V{szligbeta} subset expansions in individual volunteers (V{szligbeta} 2, 5.1, 8, 17, and 22 in volunteer 1; V{szligbeta} 1, 2, 5.1, 14, 17, and 22 in volunteer 2; and V{szligbeta} 3, 8, 14, and 16 in volunteer 3). These subsets were antigen specific, as shown by cytotoxicity and IFN-γ secretion assays on V{szligbeta} sorted cells and on T-cell clones derived from these volunteers. Moreover, eight-color flow cytometric analysis showed that these clones exhibited a T effector memory phenotype (i.e., CCR7– CD27– CD45RO+ CD62L–) and coexpressed gut homing molecules (e.g., high levels of integrin α4{szligbeta}7, intermediate levels of CCR9, and low levels of CD103). In conclusion, our results show that long-term T-cell responses to serovar Typhi in Ty21a vaccinees are oligoclonal, involving multiple TCR V{szligbeta} families. Moreover, these serovar Typhi-specific CD8+ T cells bearing defined V{szligbeta} specificities are phenotypically and functionally consistent with T effector memory cells with preferential gut homing potential.