Bacillus Calmette-Guerin vaccination of human newborns induces T cells with complex cytokine and phenotypic profiles

AP Soares, TJ Scriba, S Joseph… - The Journal of …, 2008 - journals.aai.org
AP Soares, TJ Scriba, S Joseph, R Harbacheuski, RA Murray, SJ Gelderbloem, A Hawkridge…
The Journal of Immunology, 2008journals.aai.org
The immune response to vaccination with bacillus Calmette-Guérin (BCG), the only
tuberculosis vaccine available, has not been fully characterized. We used multiparameter
flow cytometry to examine specific T cell cytokine production and phenotypic profiles in
blood from 10-wk-old infants routinely vaccinated with BCG at birth. Ex vivo stimulation of
whole blood with BCG for 12 h induced expression of predominantly IFN-γ, IL-2, and TNF-α
in CD4+ T cells in seven distinct cytokine combinations. IL-4 and IL-10 expression was …
Abstract
The immune response to vaccination with bacillus Calmette-Guérin (BCG), the only tuberculosis vaccine available, has not been fully characterized. We used multiparameter flow cytometry to examine specific T cell cytokine production and phenotypic profiles in blood from 10-wk-old infants routinely vaccinated with BCG at birth. Ex vivo stimulation of whole blood with BCG for 12 h induced expression of predominantly IFN-γ, IL-2, and TNF-α in CD4+ T cells in seven distinct cytokine combinations. IL-4 and IL-10 expression was detected in CD4+ T cells at low frequencies and only in cells that did not coexpress type 1 cytokines. Specific CD8+ T cells were less frequent than CD4+ T cells and produced mainly IFN-γ and/or IL-2 and less TNF-α, IL-4, and IL-10. Importantly, many mycobacteria-specific CD4+ and CD8+ T cells did not produce IFN-γ. The predominant phenotype of BCG-specific type 1 T cells was that of effector cells, ie, CD45RA− CCR7− CD27+, which may reflect persistence of Mycobacterium bovis BCG in infants until 10 wk of age. Among five phenotypic patterns of CD4+ T cells, central memory cells were more likely to be IL-2+ and effector cells were more likely to be IFN-γ+. We concluded that neonatal vaccination with BCG induces T cells with a complex pattern of cytokine expression and phenotypes. Measuring IFN-γ production alone underestimates the magnitude and complexity of the host cytokine response to BCG vaccination and may not be an optimal readout in studies of BCG and novel tuberculosis vaccination.
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