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Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis
G Hodge1, J W Upham2, A B Chang3
1Lung Research, Hanson Institute and Dept. Thoracic Medicine, Royal Adelaide Hospital, Adelaide, Australia.
Insights
Childhood bronchiectasis involves increased systemic pro-inflammatory and cytotoxic lymphocytes in the blood, particularly in Indigenous children. Further research is needed to link these elevated cell levels to future health conditions.
Area of Science:
- Immunology
- Pediatric Pulmonology
- Systemic Inflammation
Background:
- Bronchiectasis (BE) is prevalent in Australian Indigenous children, yet systemic inflammation is poorly understood.
- Specific pro-inflammatory and cytotoxic lymphocyte subsets (T-cells, NK cells, NKT-like cells) roles are unclear in childhood BE.
- Previous studies show elevated cytotoxic/inflammatory mediators in adult lung diseases.
Purpose of the Study:
- To investigate systemic inflammation in children with bronchiectasis.
- To quantify pro-inflammatory and cytotoxic mediators in specific lymphocyte subsets.
- To compare these changes between Indigenous and non-Indigenous children with BE.
Main Methods:
- Flow cytometry analyzed intracellular mediators (perforin, granzyme b) and cytokines (IFNγ, TNFα).
- Samples were from blood and bronchoalveolar lavage (BAL) of 12 children with BE and 10 controls.
- T cell subsets, NKT-like cells, and NK cells were examined.
Main Results:
- Children with BE showed significantly higher percentages of CD8+ T cells and T/NKT-like subsets expressing perforin/granzyme and IFNγ/TNFα in blood.
- Indigenous children with BE had a further increase in pro-inflammatory cytotoxic T cells compared to non-Indigenous children.
- No significant changes in these mediators were observed in BAL samples.
Conclusions:
- Childhood bronchiectasis is linked to heightened systemic pro-inflammatory and cytotoxic lymphocytes in peripheral blood.
- Elevated levels of these cells may indicate increased risk for future comorbidities.
- Further studies are warranted to explore the predictive value of these inflammatory markers.
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.
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