Immunization of volunteers with Salmonella enterica serovar Typhi strain Ty21a elicits the oligoclonal expansion of CD8+ T cells with predominant Vbeta 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-gamma) 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 (Vbeta) 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 Vbeta usage varied among volunteers, we identified oligoclonal Vbeta subset expansions in individual volunteers (Vbeta 2, 5.1, 8, 17, and 22 in volunteer 1; Vbeta 1, 2, 5.1, 14, 17, and 22 in volunteer 2; and Vbeta 3, 8, 14, and 16 in volunteer 3). These subsets were antigen specific, as shown by cytotoxicity and IFN-gamma secretion assays on Vbeta 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 alpha4beta7, 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 Vbeta families. Moreover, these serovar Typhi-specific CD8(+) T cells bearing defined Vbeta specificities are phenotypically and functionally consistent with T effector memory cells with preferential gut homing potential.
Salerno-Gonçalves
Rosângela
R
Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, HSF 480, Baltimore, MD 21201, USA. rsalerno@medicine.umaryland.edu
Wahid
Rezwanul
R
Sztein
Marcelo B
MB
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D007114:Immunization; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D012485:Salmonella typhi / Q000276:immunology*; D014436:Typhoid-Paratyphoid Vaccines / Q000276:immunology*
D000942:Antigens, Bacterial; D011135:Polysaccharides, Bacterial; C072772:Ty21a typhoid vaccine; D014436:Typhoid-Paratyphoid Vaccines; D007371:Interferon-gamma