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Infection and Immunity, June 2005, p. 3521-3530, Vol. 73, No. 6
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.6.3521-3530.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

Center for Vaccine Development, Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland

Received 24 September 2004/ Returned for modification 10 January 2005/ Accepted 1 February 2005

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-) 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 (Vß) 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 Vß usage varied among volunteers, we identified oligoclonal Vß subset expansions in individual volunteers (Vß 2, 5.1, 8, 17, and 22 in volunteer 1; Vß 1, 2, 5.1, 14, 17, and 22 in volunteer 2; and Vß 3, 8, 14, and 16 in volunteer 3). These subsets were antigen specific, as shown by cytotoxicity and IFN- secretion assays on Vß 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 4ß7, 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 Vß families. Moreover, these serovar Typhi-specific CD8⁺ T cells bearing defined Vß specificities are phenotypically and functionally consistent with T effector memory cells with preferential gut homing potential.

Editor: J. D. Clements

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