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

G Hodge, John Upham, Anne Chang, Katherine Baines, Stephanie Yerkovich, Susan Pizzutto, S Hodge

    Research output: Contribution to journalArticleResearchpeer-review

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    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 (IFN? and TNF?) 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 IFN? and TNF? 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. Copyright: � 2015 Hodge et al.
    Original languageEnglish
    Article numbere0133695
    Pages (from-to)1-13
    Number of pages13
    JournalPLoS One
    Volume10
    Issue number8
    DOIs
    Publication statusPublished - 2015

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    Bronchiectasis
    T-cells
    Lymphocytes
    Granzymes
    Perforin
    Blood
    lymphocytes
    blood
    T-lymphocytes
    Dimercaprol
    natural killer cells
    Pulmonary diseases
    Flow cytometry
    T-Lymphocytes
    Natural Killer Cells
    Natural Killer T-Cells
    Cytokines
    Lymphocyte Subsets
    T-Lymphocyte Subsets
    cells

    Cite this

    Hodge, G., Upham, J., Chang, A., Baines, K., Yerkovich, S., Pizzutto, S., & Hodge, S. (2015). Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis. PLoS One, 10(8), 1-13. [e0133695 ]. https://doi.org/10.1371/journal.pone.0133695
    Hodge, G ; Upham, John ; Chang, Anne ; Baines, Katherine ; Yerkovich, Stephanie ; Pizzutto, Susan ; Hodge, S. / Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis. In: PLoS One. 2015 ; Vol. 10, No. 8. pp. 1-13.
    @article{28c12243149a435ebe625f5167594662,
    title = "Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis",
    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 (IFN? and TNF?) 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 IFN? and TNF? 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. Copyright: � 2015 Hodge et al.",
    keywords = "C reactive protein, gamma interferon, granzyme B, perforin, tumor necrosis factor alpha, Article, bacterium detection, bronchiectasis, CD4 lymphocyte count, CD4+ T lymphocyte, CD8+ T lymphocyte, child, childhood disease, clinical article, controlled study, cytokine production, cytotoxic lymphocyte, enzyme blood level, enzyme synthesis, ethnic difference, female, flow cytometry, human, human tissue, Indigenous Australian, inflammatory cell, lung lavage, lymphocyte count, male, Moraxella catarrhalis, natural killer cell, natural killer T cell, preschool child, protein blood level, protein expression, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae",
    author = "G Hodge and John Upham and Anne Chang and Katherine Baines and Stephanie Yerkovich and Susan Pizzutto and S Hodge",
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    year = "2015",
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    Hodge, G, Upham, J, Chang, A, Baines, K, Yerkovich, S, Pizzutto, S & Hodge, S 2015, 'Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis', PLoS One, vol. 10, no. 8, e0133695 , pp. 1-13. https://doi.org/10.1371/journal.pone.0133695

    Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis. / Hodge, G; Upham, John; Chang, Anne; Baines, Katherine; Yerkovich, Stephanie; Pizzutto, Susan; Hodge, S.

    In: PLoS One, Vol. 10, No. 8, e0133695 , 2015, p. 1-13.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Increased Peripheral Blood Pro-Inflammatory/Cytotoxic Lymphocytes in Children with Bronchiectasis

    AU - Hodge, G

    AU - Upham, John

    AU - Chang, Anne

    AU - Baines, Katherine

    AU - Yerkovich, Stephanie

    AU - Pizzutto, Susan

    AU - Hodge, S

    N1 - NHMRC Grant No 1042601 1040830 1058552 1058213 1038415

    PY - 2015

    Y1 - 2015

    N2 - 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 (IFN? and TNF?) 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 IFN? and TNF? 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. Copyright: � 2015 Hodge et al.

    AB - 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 (IFN? and TNF?) 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 IFN? and TNF? 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. Copyright: � 2015 Hodge et al.

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