Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis

PLoS One. 2015 Aug 10;10(8):e0133695. doi: 10.1371/journal.pone.0133695. eCollection 2015.

Abstract

Objective: Bronchiectasis (BE) in children is common in some communities including Indigenous children in Australia. Relatively little is known about the nature of systemic inflammation in these children, especially the contribution of specific pro-inflammatory and cytotoxic lymphocyte subsets: T-cells, natural killer (NK) cells and NKT-like cells. We have shown that these cells produce increased cytotoxic (granzyme b and perforin) and inflammatory (IFNγ and TNFα) mediators in several adult chronic lung diseases and hypothesised that similar changes would be evident in children with BE.

Methods: Intracellular cytotoxic mediators perforin and granzyme b and pro-inflammatory cytokines were measured in T cell subsets, NKT-like and NK cells from blood and bronchoalveolar samples from 12 children with BE and 10 aged-matched control children using flow cytometry.

Results: There was a significant increase in the percentage of CD8+ T cells and T and NKT-like subsets expressing perforin/granzyme and IFNγ and TNFα in blood in BE compared with controls. There was a further increase in the percentage of pro-inflammatory cytotoxic T cells in Indigenous compared with non-Indigenous children. There was no change in any of these mediators in BAL.

Conclusions: Childhood bronchiectasis is associated with increased systemic pro-inflammatory/cytotoxic lymphocytes in the peripheral blood. Future studies need to examine the extent to which elevated levels of pro-inflammatory cytotoxic cells predict future co-morbidities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Australia
  • Bronchiectasis / blood*
  • Bronchoalveolar Lavage Fluid
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Flow Cytometry
  • Granzymes / blood
  • Humans
  • Infant
  • Inflammation / blood*
  • Interferon-gamma / blood
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / cytology
  • Male
  • Perforin / blood
  • Population Groups
  • T-Lymphocytes / cytology
  • T-Lymphocytes, Cytotoxic / cytology*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Perforin
  • Interferon-gamma
  • Granzymes

Grants and funding

This study was funded by a Channel 7 grant (13688), NHMRC project grant 1042601 and supported by NHMRC CRE for Lung Health of Aboriginal and Torres Strait Islander children grant 1040830. PG (grant 1058552) and AC (grant 1058213) are supported by NHMRC fellowships, SP by a NHMRC post-graduate scholarship (1038415). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.