Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Booth, Jayaum S, Goldberg, Eric, Patil, Seema A, Barnes, Robin S, Greenwald, Bruce D, Sztein, Marcelo B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376105/
https://www.ncbi.nlm.nih.gov/pubmed/30346608
http://dx.doi.org/10.1093/intimm/dxy070
_version_ 1783395492771659776
author Booth, Jayaum S
Goldberg, Eric
Patil, Seema A
Barnes, Robin S
Greenwald, Bruce D
Sztein, Marcelo B
author_facet Booth, Jayaum S
Goldberg, Eric
Patil, Seema A
Barnes, Robin S
Greenwald, Bruce D
Sztein, Marcelo B
author_sort Booth, Jayaum S
collection PubMed
description 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); IFNγ 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.
format Online
Article
Text
id pubmed-6376105
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-63761052019-02-21 Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4(+) T memory responses in humans Booth, Jayaum S Goldberg, Eric Patil, Seema A Barnes, Robin S Greenwald, Bruce D Sztein, Marcelo B Int Immunol Original Research 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); IFNγ 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. Oxford University Press 2018-10-20 /pmc/articles/PMC6376105/ /pubmed/30346608 http://dx.doi.org/10.1093/intimm/dxy070 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of The Japanese Society for Immunology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research
Booth, Jayaum S
Goldberg, Eric
Patil, Seema A
Barnes, Robin S
Greenwald, Bruce D
Sztein, Marcelo B
Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4(+) T memory responses in humans
title Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4(+) T memory responses in humans
title_full Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4(+) T memory responses in humans
title_fullStr Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4(+) T memory responses in humans
title_full_unstemmed Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4(+) T memory responses in humans
title_short Effect of the live oral attenuated typhoid vaccine, Ty21a, on systemic and terminal ileum mucosal CD4(+) T memory responses in humans
title_sort effect of the live oral attenuated typhoid vaccine, ty21a, on systemic and terminal ileum mucosal cd4(+) t memory responses in humans
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376105/
https://www.ncbi.nlm.nih.gov/pubmed/30346608
http://dx.doi.org/10.1093/intimm/dxy070
work_keys_str_mv AT boothjayaums effectoftheliveoralattenuatedtyphoidvaccinety21aonsystemicandterminalileummucosalcd4tmemoryresponsesinhumans
AT goldbergeric effectoftheliveoralattenuatedtyphoidvaccinety21aonsystemicandterminalileummucosalcd4tmemoryresponsesinhumans
AT patilseemaa effectoftheliveoralattenuatedtyphoidvaccinety21aonsystemicandterminalileummucosalcd4tmemoryresponsesinhumans
AT barnesrobins effectoftheliveoralattenuatedtyphoidvaccinety21aonsystemicandterminalileummucosalcd4tmemoryresponsesinhumans
AT greenwaldbruced effectoftheliveoralattenuatedtyphoidvaccinety21aonsystemicandterminalileummucosalcd4tmemoryresponsesinhumans
AT szteinmarcelob effectoftheliveoralattenuatedtyphoidvaccinety21aonsystemicandterminalileummucosalcd4tmemoryresponsesinhumans