The Journal of infectious diseases · 2013
Longitudinal changes in CD4(+) T-cell memory responses induced by BCG vaccination of newborns.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Soares Andreia P, Kwong Chung Cheong K C, Choice Terry, Hughes E Jane, Jacobs Gail, van Rensburg Esme Janse, Khomba Gloria, de Kock Marwou, Lerumo Lesedi, Makhethe Lebohang, Maneli Mbulelo H, Pienaar Bernadette, Smit Erica, Tena-Coki Nontobeko G, van Wyk Leandre, Boom W Henry, Kaplan Gilla, Scriba Thomas J, Hanekom Willem A
Аннотация
BACKGROUND: Improved vaccination strategies against tuberculosis are needed, such as approaches to boost immunity induced by the current vaccine, BCG. Design of these strategies has been hampered by a lack of knowledge of the kinetics of the human host response induced by neonatal BCG vaccination. Furthermore, the functional and phenotypic attributes of BCG-induced long-lived memory T-cell responses remain unclear.
METHODS: We assessed the longitudinal CD4 T-cell response following BCG vaccination of human newborns. The kinetics, function, and phenotype of these cells were measured using flow cytometric whole-blood assays.
RESULTS: We showed that the BCG-specific CD4 T-cell response peaked 6-10 weeks after vaccination and gradually waned over the first year of life. Highly activated T-helper 1 cells, predominantly expressing interferon γ, tumor necrosis factor α, and/or interleukin 2, were present at the peak response. Following contraction, BCG-specific CD4 T cells expressed high levels of Bcl-2 and displayed a predominant CD45RACCR7 central memory phenotype. However, cytokine and cytotoxic marker expression by these cells was more characteristic of effector memory cells.
CONCLUSIONS: Our findings suggest that boosting of BCG-primed CD4 T cells with heterologous tuberculosis vaccines may be best after 14 weeks of age, once an established memory response has developed.
METHODS: We assessed the longitudinal CD4 T-cell response following BCG vaccination of human newborns. The kinetics, function, and phenotype of these cells were measured using flow cytometric whole-blood assays.
RESULTS: We showed that the BCG-specific CD4 T-cell response peaked 6-10 weeks after vaccination and gradually waned over the first year of life. Highly activated T-helper 1 cells, predominantly expressing interferon γ, tumor necrosis factor α, and/or interleukin 2, were present at the peak response. Following contraction, BCG-specific CD4 T cells expressed high levels of Bcl-2 and displayed a predominant CD45RACCR7 central memory phenotype. However, cytokine and cytotoxic marker expression by these cells was more characteristic of effector memory cells.
CONCLUSIONS: Our findings suggest that boosting of BCG-primed CD4 T cells with heterologous tuberculosis vaccines may be best after 14 weeks of age, once an established memory response has developed.
Предметные рубрики MeSH
BCG VaccineBiomarkersCD4-Positive T-LymphocytesCross-Sectional StudiesFemaleFlow CytometryHumansImmunologic MemoryInfant, NewbornInterferon-gammaInterleukin-2Longitudinal StudiesLymphocyte ActivationMaleMycobacterium tuberculosisPhenotypeTime FactorsTreatment OutcomeTuberculosisTumor Necrosis Factor-alphaVaccination