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Targeting peripheral blood pro-inflammatory CD28null T cells and natural killer T-like cells by inhibiting CD137 expression: possible relevance to treatment of bronchiolitis obliterans syndrome.
J Heart Lung Transplant. 2013 Nov; 32(11):1081-9.JH

Abstract

BACKGROUND

We have shown that bronchiolitis obliterans syndrome (BOS) is associated with attenuated suppression of pro-inflammatory cytokines and granzyme B by steroid-resistant peripheral blood CD28nullCD137+ T cells and natural killer T (NKT)-like cells. We hypothesized that we could target these steroid-resistant lymphocytes by inhibiting costimulation through CD137.

METHODS

Isolated peripheral blood mononuclear cells from transplant patients with stable lung function, patients with BOS, and healthy controls were stimulated with anti-CD3 with and without blocking anti-CD137 and with and without 10(-6) mol/liter methylprednisolone (MP) (with and without stimulatory anti-CD137). Pro-inflammatory cytokine profiles and expression of the cytotoxic mediator, granzyme B, by CD28null T and NKT-like cells were determined using flow cytometry.

RESULTS

There was a significant decrease in the percentage of CD28null T and NKT-like cells producing interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and granzyme B in all individuals in the presence of anti-CD137 blocking antibody compared with anti-CD3 alone (eg, 30% decrease in CD8+CD28null TNF-α+ cells). Stimulatory anti-CD137 was associated with an increase in pro-inflammatory/cytotoxic cells. Treatment with anti-CD137 blocking with prednisolone further reduced IFN-γ, TNF-α, and granzyme B in these cells.

CONCLUSIONS

Blocking CD137 expression in CD28null T cells and NKT-like cells is associated with down-regulation of IFN-γ, TNF-α, and granzyme B. Targeting CD137 reduces pro-inflammatory/cytotoxic expression in steroid-resistant CD28null T and NKT-like cells and may have therapeutic implications for patients with BOS.

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Authors+Show Affiliations

Hodge G
Lung Research, Hanson Institute, Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, Australia; Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA 5000, Australia; South Australian Lung Transplant Service, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: greg.hodge@health.sa.gov.au.
Hodge S
No affiliation info available
Reynolds PN
No affiliation info available
Holmes M
No affiliation info available

MeSH

AdultAntibodiesBronchiolitis ObliteransCD28 AntigensCase-Control StudiesCells, CulturedGranzymesHumansInterferon-gammaKiller Cells, NaturalLeukocytes, MononuclearLung TransplantationMethylprednisoloneMiddle AgedPostoperative ComplicationsT-LymphocytesTumor Necrosis Factor Receptor Superfamily, Member 9Tumor Necrosis Factor-alpha

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24021943

Citation

Hodge, Greg, et al. "Targeting Peripheral Blood Pro-inflammatory CD28null T Cells and Natural Killer T-like Cells By Inhibiting CD137 Expression: Possible Relevance to Treatment of Bronchiolitis Obliterans Syndrome." The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, vol. 32, no. 11, 2013, pp. 1081-9.
Hodge G, Hodge S, Reynolds PN, et al. Targeting peripheral blood pro-inflammatory CD28null T cells and natural killer T-like cells by inhibiting CD137 expression: possible relevance to treatment of bronchiolitis obliterans syndrome. J Heart Lung Transplant. 2013;32(11):1081-9.
Hodge, G., Hodge, S., Reynolds, P. N., & Holmes, M. (2013). Targeting peripheral blood pro-inflammatory CD28null T cells and natural killer T-like cells by inhibiting CD137 expression: possible relevance to treatment of bronchiolitis obliterans syndrome. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 32(11), 1081-9. https://doi.org/10.1016/j.healun.2013.07.017
Hodge G, et al. Targeting Peripheral Blood Pro-inflammatory CD28null T Cells and Natural Killer T-like Cells By Inhibiting CD137 Expression: Possible Relevance to Treatment of Bronchiolitis Obliterans Syndrome. J Heart Lung Transplant. 2013;32(11):1081-9. PubMed PMID: 24021943.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting peripheral blood pro-inflammatory CD28null T cells and natural killer T-like cells by inhibiting CD137 expression: possible relevance to treatment of bronchiolitis obliterans syndrome. AU - Hodge,Greg, AU - Hodge,Sandra, AU - Reynolds,Paul N, AU - Holmes,Mark, Y1 - 2013/09/07/ PY - 2013/04/10/received PY - 2013/07/09/revised PY - 2013/07/18/accepted PY - 2013/9/12/entrez PY - 2013/9/12/pubmed PY - 2014/6/11/medline KW - BOS KW - CD28null T cells KW - IFN-γ KW - TNF-α KW - blocking CD137 KW - lung transplant SP - 1081 EP - 9 JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JO - J Heart Lung Transplant VL - 32 IS - 11 N2 - BACKGROUND: We have shown that bronchiolitis obliterans syndrome (BOS) is associated with attenuated suppression of pro-inflammatory cytokines and granzyme B by steroid-resistant peripheral blood CD28nullCD137+ T cells and natural killer T (NKT)-like cells. We hypothesized that we could target these steroid-resistant lymphocytes by inhibiting costimulation through CD137. METHODS: Isolated peripheral blood mononuclear cells from transplant patients with stable lung function, patients with BOS, and healthy controls were stimulated with anti-CD3 with and without blocking anti-CD137 and with and without 10(-6) mol/liter methylprednisolone (MP) (with and without stimulatory anti-CD137). Pro-inflammatory cytokine profiles and expression of the cytotoxic mediator, granzyme B, by CD28null T and NKT-like cells were determined using flow cytometry. RESULTS: There was a significant decrease in the percentage of CD28null T and NKT-like cells producing interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and granzyme B in all individuals in the presence of anti-CD137 blocking antibody compared with anti-CD3 alone (eg, 30% decrease in CD8+CD28null TNF-α+ cells). Stimulatory anti-CD137 was associated with an increase in pro-inflammatory/cytotoxic cells. Treatment with anti-CD137 blocking with prednisolone further reduced IFN-γ, TNF-α, and granzyme B in these cells. CONCLUSIONS: Blocking CD137 expression in CD28null T cells and NKT-like cells is associated with down-regulation of IFN-γ, TNF-α, and granzyme B. Targeting CD137 reduces pro-inflammatory/cytotoxic expression in steroid-resistant CD28null T and NKT-like cells and may have therapeutic implications for patients with BOS. SN - 1557-3117 UR - https://www.unboundmedicine.com/medline/citation/24021943/Targeting_peripheral_blood_pro_inflammatory_CD28null_T_cells_and_natural_killer_T_like_cells_by_inhibiting_CD137_expression:_possible_relevance_to_treatment_of_bronchiolitis_obliterans_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1053-2498(13)01357-0 DB - PRIME DP - Unbound Medicine ER -