Article
Interleukin-7 enhanced antigen-specific T-cell immunity is a marker for disease severity and recovery in children with tuberculosis and correlates with soluble Interleukin-7 receptor expression
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Published: | March 28, 2013 |
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Immunity biomarkers that predict susceptibility against recurrent tuberculosis are missing. Failure to develop effective T-cell memory during active disease and recovery may account for increased susceptibility against recurrent disease. Pathogen persistence and the accessibility of key cytokines, predominantly Interleukin-7 (IL-7) are possible reasons for non-protective memory. Here we aim at characterizing the role of IL-7 and the soluble IL-7 receptor (sIL-7R) for the induction of protective T-cell immunity against tuberculosis.
We recruited 22 children with ‚mild’ and ‚severe’ manifestations of tuberculosis, as well as healthy M. tuberculosis infected (LTBI) (14) and non-infected children (19). Peripheral blood samples were taken on diagnosis, under treatment (day 90) and after treatment completion (day 365). Interferon-γ (IFNγ) release assays (IGRA), IL-7 dependent antigen-specific in vitro re-stimulation, T-cell phenotyping and sIL-7R quantification in plasma samples were performed.
IL-7 increased the proportions of IFNγ expressing T cells induced by purified protein derivative (PPD) of M. tuberculosis in children with LTBI (p=0.004) and in children with tuberculosis after completion of treatment (p=0.008), but did not have a significant effect in children with tuberculosis prior to chemotherapy. IL-7 induced IFNγ positive T-cell proportions increased in children with tuberculosis after completion of treatment (p = 0.021), but there was no marked increase in the subgroup of children with severe manifestations of disease. Notably, sIL-7R concentrations in plasma correlated positively (r = 0.436, p = 0.02) with in vitro IFNγ expression in response to IL-7.
We concluded that antigen-specific T cells from children with tuberculosis tend to respond worse to IL-7 administration in vitro and that improved IL-7 reactivity - accompanied by increased sIL-7R expression in plasma - is a marker of recovery in children with mild disease. Because of the central role of IL-7 in the generation of protective memory T cells, we hypothesized that these differences may also reflect the susceptibility to recurrent disease. Future studies will address these questions in tuberculosis high incidence countries.