Dynamics of the CD8 T-cell response following yellow fever virus 17D immunization

被引:32
作者
Co, Mary Dawn T. [1 ]
Kilpatrick, Elizabeth D. [1 ]
Rothman, Alan L. [1 ]
机构
[1] Univ Massachusetts, Sch Med, Ctr Infect Dis & Vaccine Res, Worcester, MA USA
关键词
CD8 T cells; human; vaccine; viral; yellow fever; HEPATITIS-C VIRUS; LYMPHOCYTE RESPONSES; REPERTOIRE DIVERSITY; FUNCTIONAL-HETEROGENEITY; SMALLPOX VACCINATION; IMMUNE-RESPONSES; VIRAL-INFECTION; VACCINIA VIRUS; HUMAN EFFECTOR; MEMORY CELLS;
D O I
10.1111/j.1365-2567.2009.03070.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
P>Management of yellow fever is focused on the prevention of illness by the use of the yellow fever virus (YFV) 17D vaccine. The role of neutralizing antibodies in protection is generally accepted with YFV-specific T cells likely contributing to the control of viral replication. We studied CD8(+) T-cell responses to four defined human leucocyte antigen-B35-restricted epitopes in YFV vaccine recipients as a model of the kinetics of cytotoxic T-lymphocyte responses to an acute human viral infection. Multiple features of these epitope-specific responses were analysed after vaccination including magnitude, cytokine production, phenotype and T-cell receptor repertoire. Peak peptide-specific interferon-gamma (IFN-gamma) responses of almost 1% of CD8(+) T cells were seen as early as 2 weeks post-vaccination; however, dominant responses varied between donors. Peptide-specific responses were still detectable at 54 months post-vaccination. Tetramer-positive cells, at high frequencies, were detected as early as 7-9 days, before detectable IFN-gamma-producing cells, suggesting a defect in the functional capacity of some antigen-specific cells early post-vaccination. The predominant memory phenotype of the tetramer-positive population was a differentiated effector (CD45RA(+) CCR7(-) CD62L(-)) phenotype. The T-cell receptor V beta analysis revealed a diverse oligoclonal repertoire in tetramer-positive T-cell populations in two individuals. These characteristics of the YFV-specific T-cell response could contribute to vaccine effectiveness.
引用
收藏
页码:e718 / e727
页数:10
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