Diversity of Salmonella Typhi-responsive CD4 and CD8 T cells before and after Ty21a typhoid vaccination in children and adults.
Int Immunol
; 31(5): 315-333, 2019 04 26.
Article
em En
| MEDLINE
| ID: mdl-30951606
ABSTRACT
Typhoid fever is a life-threatening disease caused by the human-restricted pathogen Salmonella enterica serovar Typhi (S. Typhi). The oral live attenuated Ty21a typhoid vaccine protects against this severe disease by eliciting robust, multifunctional cell-mediated immunity (CMI), shown to be associated with protection in wild-type S. Typhi challenge studies. Ty21a induces S. Typhi-responsive CD8+ and CD4+ T cells but little is known about the response to this vaccine in children. To address this important gap in knowledge, we have used mass cytometry to analyze pediatric and adult pre- and post-Ty21a vaccination CMI in an autologous S. Typhi antigen presentation model. Here, using conventional supervised analytical tools, we show adult T cells are more multifunctional at baseline than those obtained from children. Moreover, pediatric and adult T cells respond similarly to Ty21a vaccination, but adult responders remain more multifunctional. The use of the unsupervised dimensionality reduction tool tSNE (t-distributed Stochastic Neighbor Embedding) allowed us to confirm these findings, as well as to identify increases and decreases in well-defined specific CD4+ and CD8+ T-cell populations that were not possible to uncover using the conventional gating strategies. These findings evidenced age-associated maturation of multifunctional S. Typhi-responsive T-cell populations, including those which we have previously shown to be associated with protection from, and/or delayed onset of, typhoid disease. These findings are likely to play an important role in improving pediatric vaccination strategies against S. Typhi and other enteric pathogens.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polissacarídeos Bacterianos
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Salmonella typhi
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Vacinas Tíficas-Paratíficas
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Linfócitos T CD4-Positivos
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Linfócitos T CD8-Positivos
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
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Adult
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Aged
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Int Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos