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    Association between S. Typhi-specific memory CD4+ and CD8+ T responses in the terminal ileum mucosa and in peripheral blood elicited by the live oral typhoid vaccine Ty21a in humans

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    Author
    Booth, Jayaum S.
    Goldberg, Eric
    Patil, Seema A.
    Greenwald, Bruce D.
    Sztein, Marcelo B.
    Date
    2019-03-03
    Journal
    Human Vaccines and Immunotherapeutics
    Publisher
    Taylor and Francis Inc.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://www.doi.org/10.1080/21645515.2018.1564570
    Abstract
    CD4+ and CD8+ T subsets are essential components of the adaptive immune system which act in concert at the site of infections to effectively protect against pathogens. Very limited data is available in humans regarding the relationship between CD4+ and CD8+ S. Typhi responsive cells in the terminal ileum mucosa (TI) and peripheral blood following Ty21a oral typhoid immunization. Here, we compared TI lamina propria mononuclear cells (LPMC) and peripheral blood CD4+ and CD8+ T memory (TM) subsets responses and their relationship by Spearman’s correlation following Ty21a immunization in volunteers undergoing routine colonoscopy. We observed that Ty21a immunization (i) influences the homing and accumulation of both CD4+ and CD8+ T cells in the TI, particularly integrin α4β7+ CCR9+ CD8+ T cells, (ii) elicits significantly higher frequencies of LPMC S. Typhi-responsive CD8+ T multifunctional (CD107a, IFNγ, IL-17A and/or MIP1β) cells than their CD4+ T counterparts, and (iii) results in the correlation of LPMC CD4+ Teffector/memory (TEM) S. Typhi responses (CD107a, IFNγ, TNFα, IL-17A and/or MIP1β) to their LPMC CD8+ TEM counterparts. Moreover, we demonstrated that these positive correlations between CD4+ and CD8+ TEM occur primarily in TI LPMC but not in PBMC, suggesting important differences in responses between the mucosal and systemic compartments following oral Ty21a immunization. This study provides the first demonstration of the correlation of S. Typhi-specific CD4+ and CD8+ TM responses in the human terminal ileum mucosa and provides valuable information regarding the generation of mucosal and systemic immune responses following oral Ty21a-immunization which might impact future vaccine design and development. © 2019, © 2019 The Author(s).
    Sponsors
    This work was funded 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]).
    Keyword
    Lamina propria mononuclear cells
    PBMC
    S. Typhi specific
    T cells
    Ty21a immunization
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068894208&origin=inward; http://hdl.handle.net/10713/10120
    ae974a485f413a2113503eed53cd6c53
    10.1080/21645515.2018.1564570
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