Document Detail


Ex Vivo kinetics of early and long-term multifunctional human leukocyte antigen E-specific CD8+ cells in volunteers immunized with the Ty21a typhoid vaccine.
MedLine Citation:
PMID:  20660136     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
T cells are likely to play an important role in the host defense against Salmonella enterica serovar Typhi, the causative agent of typhoid fever. We have shown that HLA-E can function as a restriction element for S. Typhi-specific CD8(+) T cells. Because of the potential importance of HLA-E-restricted CD8(+) responses in resistance to Salmonella infection, we characterized these responses and investigated their kinetics of appearance and persistence in volunteers immunized orally with the licensed attenuated Ty21a strain typhoid vaccine. Cells were obtained from volunteers before and at days 2, 4, 7, 10, 14, 28, 42, 56, 120, 180, 360, and 720 after immunization. An ex vivo multicolor staining panel including antibodies to CD107a and -b, interleukin-2, gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) was used to functionally assess memory T-cell subsets by flow cytometry. Increases in cytokine-secreting CD8(+) cells were observed in the T effector/memory (T(EM)) and CD45RA(+) T(EM) (T(EMRA)) subsets as early as 4 days after immunization and persisted, particularly in the T(EMRA) subset, up to 2 years after immunization. The majority of HLA-E-restricted CD8(+) cells 28 to 56 days after immunization coexpressed CD107, IFN-gamma, and TNF-alpha, showing characteristic features of multifunctional T cells. In summary, the multifunctionality and longevity of the HLA-E-restricted CD8 responses observed in this study highlight their significance in adaptive immunity to S. Typhi. Finally, this is the first demonstration, in either animals or humans, of the presence of long-term multifunctional HLA-E-restricted CD8(+) cells after immunization.
Authors:
Rosângela Salerno-Goncalves; Rezwanul Wahid; Marcelo B Sztein
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-07-21
Journal Detail:
Title:  Clinical and vaccine immunology : CVI     Volume:  17     ISSN:  1556-679X     ISO Abbreviation:  Clin. Vaccine Immunol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-02     Completed Date:  2010-12-08     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  101252125     Medline TA:  Clin Vaccine Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1305-14     Citation Subset:  IM    
Affiliation:
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201, USA. rsalerno@medicine.umaryland.edu
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adult
CD8-Positive T-Lymphocytes / chemistry,  immunology*
Flow Cytometry
HLA Antigens / analysis*
Histocompatibility Antigens Class I / analysis*
Human Experimentation
Humans
Interferon-gamma / biosynthesis
Interleukin-2 / biosynthesis
Lysosomal-Associated Membrane Protein 1 / analysis
Lysosomal-Associated Membrane Protein 2 / analysis
Polysaccharides, Bacterial / administration & dosage,  immunology*
T-Lymphocyte Subsets / chemistry,  immunology*
Tumor Necrosis Factor-alpha / biosynthesis
Typhoid Fever / prevention & control*
Typhoid-Paratyphoid Vaccines / administration & dosage,  immunology*
Grant Support
ID/Acronym/Agency:
R01 AI036525/AI/NIAID NIH HHS; U19 AI082655/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/HLA Antigens; 0/HLA-E antigen; 0/Histocompatibility Antigens Class I; 0/Interleukin-2; 0/Lysosomal-Associated Membrane Protein 1; 0/Lysosomal-Associated Membrane Protein 2; 0/Polysaccharides, Bacterial; 0/Tumor Necrosis Factor-alpha; 0/Ty21a typhoid vaccine; 0/Typhoid-Paratyphoid Vaccines; 82115-62-6/Interferon-gamma
Comments/Corrections

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