Attenuated oral typhoid vaccine Ty21A elicits lamina propria and intra-epithelial lymphocyte tissue-resident effector memory CD8 T responses in the human terminal ileum
AuthorBooth, Jayaum S.
Patil, Seema A.
Barnes, Robin S.
Greenwald, Bruce D.
Sztein, Marcelo B.
JournalFrontiers in Immunology
PublisherFrontiers Media S.A.
MetadataShow full item record
AbstractTissue-resident memory T cells (TRM) are newly defined memory T cells (TM) distinct from circulating TM subsets which have the potential to mount rapid protective immune responses at the site of infection. However, very limited information is available regarding the role and contribution of TRM in vaccine-mediated immune responses in humans at the site of infection. Here, we studied the role and contribution of tissue resident memory T cells (TRM) located in the terminal ileum (TI) (favored site of infection for S. Typhi) following oral Ty21a immunization in humans. We examined TI-lamina propria mononuclear cells (LPMC) and intra-epithelial lymphocytes (IEL) CD8+ TRM subsets obtained from healthy volunteers undergoing medically-indicated colonoscopies who were either immunized with Ty21a or unvaccinated. No significant differences in the frequencies of LPMC CD8+ TRM and CD8+CD69+CD103– T cells subsets were observed following Ty21a-immunization. However, LPMC CD8+ TRM exhibited significantly higher levels of cytokines (IFN-γ, IL-17A, and TNF-α) ex-vivo in Ty21a-vaccinated than in unvaccinated volunteers. LPMC CD8+ TRM S. Typhi-specific responses were evaluated using S. Typhi-infected targets and found to produce significantly higher levels of S. Typhi-specific IL-17A. In contrast, LPMC CD8+CD69+CD103- T cells produced significantly increased S. Typhi-specific levels of IFN-γ, IL-2, and IL-17A. Finally, we assessed CD8+ TRM in IEL and observed that the frequency of IEL CD8+ TRM is significantly lower following Ty21a immunization. However, ex-vivo IEL CD8+ TRM elicited by Ty21a immunization spontaneously produced significantly higher levels of cytokines (IFN-γ, IL-17A, IL-2, and TNF-α). This study provides the first demonstration of the effect of oral Ty21a vaccination on CD8+ TRM subsets (spontaneous and S. Typhi-specific) responses in the LPMC and IEL compartment of the human terminal ileum mucosa, contributing novel information to our understanding of the generation of mucosal immune responses following oral Ty21a-immunization. Copyright © 2019 Booth, Patil, Goldberg, Barnes, Greenwald and Sztein. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
SponsorsThis 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]).
KeywordIEL intraepithelial lymphocytes
Lamina propria mononuclear cells
Mucosal immune responses
Tissue resident memory CD8+ T
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063990447&origin=inward; http://hdl.handle.net/10713/10083
- Oral typhoid vaccine Ty21a elicits antigen-specific resident memory CD4<sup>+</sup> T cells in the human terminal ileum lamina propria and epithelial compartments.
- Authors: Booth JS, Goldberg E, Barnes RS, Greenwald BD, Sztein MB
- Issue date: 2020 Feb 25
- Association between <i>S</i>. 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.
- Authors: Booth JS, Goldberg E, Patil SA, Greenwald BD, Sztein MB
- Issue date: 2019
- Systemic and Terminal Ileum Mucosal Immunity Elicited by Oral Immunization With the Ty21a Typhoid Vaccine in Humans.
- Authors: Booth JS, Patil SA, Ghazi L, Barnes R, Fraser CM, Fasano A, Greenwald BD, Sztein MB
- Issue date: 2017 Nov
- Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4+ T memory responses in humans.
- Authors: Booth JS, Goldberg E, Patil SA, Barnes RS, Greenwald BD, Sztein MB
- Issue date: 2019 Feb 15
- Cross-reactive multifunctional CD4+ T cell responses against Salmonella enterica serovars Typhi, Paratyphi A and Paratyphi B in humans following immunization with live oral typhoid vaccine Ty21a.
- Authors: Wahid R, Fresnay S, Levine MM, Sztein MB
- Issue date: 2016 Dec