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Salmonella Typhi-specific multifunctional CD8+ T cells play a dominant role in protection from typhoid fever in humans.
- Source :
-
Journal of Translational Medicine . 3/1/2016, Vol. 14, p1-14. 14p. - Publication Year :
- 2016
-
Abstract
- <bold>Background: </bold>Typhoid fever, caused by the human-restricted organism Salmonella Typhi (S. Typhi), is a major public health problem worldwide. Development of novel vaccines remains imperative, but is hampered by an incomplete understanding of the immune responses that correlate with protection.<bold>Methods: </bold>Recently, a controlled human infection model was re-established in which volunteers received ~10(3) cfu wild-type S. Typhi (Quailes strain) orally. Twenty-one volunteers were evaluated for their cell-mediated immune (CMI) responses. Ex vivo PBMC isolated before and up to 1 year after challenge were exposed to three S. Typhi-infected targets, i.e., autologous B lymphoblastoid cell-lines (B-LCL), autologous blasts and HLA-E restricted AEH B-LCL cells. CMI responses were evaluated using 14-color multiparametric flow cytometry to detect simultaneously five intracellular cytokines/chemokines (i.e., IL-17A, IL-2, IFN-g, TNF-a and MIP-1b) and a marker of degranulation/cytotoxic activity (CD107a).<bold>Results: </bold>Herein we provide the first evidence that S. Typhi-specific CD8+ responses correlate with clinical outcome in humans challenged with wild-type S. Typhi. Higher multifunctional S. Typhi-specific CD8+ baseline responses were associated with protection against typhoid and delayed disease onset. Moreover, following challenge, development of typhoid fever was accompanied by decreases in circulating S. Typhi-specific CD8+ T effector/memory (TEM) with gut homing potential, suggesting migration to the site(s) of infection. In contrast, protection against disease was associated with low or no changes in circulating S. Typhi-specific TEM.<bold>Conclusions: </bold>These studies provide novel insights into the protective immune responses against typhoid disease that will aid in selection and development of new vaccine candidates. [ABSTRACT FROM AUTHOR]
- Subjects :
- *TYPHOID fever
*SALMONELLA typhi
*CD8 antigen
*PUBLIC health
*FLOW cytometry
*GUT microbiome
*COMPARATIVE studies
*DYNAMICS
*GASTROINTESTINAL system
*IMMUNITY
*RESEARCH methodology
*MEDICAL cooperation
*RESEARCH
*RESEARCH funding
*SALMONELLA
*T cells
*EVALUATION research
*TREATMENT effectiveness
*PREVENTION
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 14
- Database :
- Academic Search Index
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 113502596
- Full Text :
- https://doi.org/10.1186/s12967-016-0819-7