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    Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4 + T memory responses in humans

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    Author
    Booth, J.S.
    Goldberg, E.
    Patil, S.A.
    Date
    2019
    Journal
    International Immunology
    Publisher
    Oxford University Press
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1093/intimm/dxy070
    Abstract
    Our current understanding of CD4 + T-cell-mediated immunity (CMI) elicited by the oral live attenuated typhoid vaccine Ty21a is primarily derived from studies using peripheral blood. Very limited data are available in humans regarding mucosal immunity (especially CD4 + T) at the site of infection (e.g. terminal ileum; TI). Here using multiparametric flow cytometry, we examined the effect of Ty21a immunization on TI-lamina propria mononuclear cells (LPMC) and peripheral blood CD4 + T memory (T M) subsets in volunteers undergoing routine colonoscopy. Interestingly, we observed significant increases in the frequencies of LPMC CD4 + T cells following Ty21a immunization, restricted to the T effector/memory (T EM)-CD45RA + (T EMRA) subset. Importantly, Ty21a immunization elicited Salmonella Typhi-responsive LPMC CD4 + T cells in all major T M subsets [interferon (IFN)γ and interleukin (IL)-17A in T EM; (IFN)γ and macrophage inflammatory protein (MIP)1β in T central/memory (T CM); and IL-2 in T EMRA ]. Subsequently, we analyzed LPMC S. Typhi-responsive CD4 + T cells in depth for multifunctional (MF) effectors. We found that LPMC CD4 + T EM responses were mostly MF, except for those cells exhibiting the characteristics associated with IL-17A responses. Finally, we compared mucosal to systemic responses and observed that LPMC CD4 + S. Typhi-specific responses were unique and distinct from their systemic counterparts. This study provides the first demonstration of S. Typhi-specific CD4 + T M responses in the human TI mucosa and provides valuable information about the generation of mucosal immune responses following oral Ty21a immunization. Copyright The Author(s) 2018. Published by Oxford University Press on behalf of The Japanese Society for Immunology.
    Sponsors
    This work was supported by NIAID, NIH, DHHS grants R01-AI036525, U19-AI082655 [Cooperative Center for Human Immunology (CCHI)] and U19-AI109776 [Center of Excellence for Translational Research (CETR)]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.
    Keyword
    CD4 + T
    lamina propria mononuclear cells
    mucosal responses
    Blood
    Typhoid Fever
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85061573766&doi=10.1093%2fintimm%2fdxy070&partnerID=40&md5=d1a7456585d2f6fdae894843bffbcc05; http://hdl.handle.net/10713/8598
    ae974a485f413a2113503eed53cd6c53
    10.1093/intimm/dxy070
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