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Increased natural killer T-like cells are a major source of pro-inflammatory cytokines and granzymes in lung transplant recipients.
Respirology. 2012 Jan; 17(1):155-63.R

Abstract

BACKGROUND AND OBJECTIVE

Natural killer T (NKT)-like cells are a small but significant population of T lymphocytes; however, their role in lung transplant and the effect of current immunosuppressive agents on their function is largely unknown. We have previously shown lung transplant rejection was associated with an increase in peripheral blood T cell γ-interferon (IFN-γ), tumour necrosis factor-α (TNF-α) and granzyme B. NKT-like cells are a source of these pro-inflammatory mediators and as such may be involved in lung transplant pathology.

METHODS

We analysed NKT-like cell numbers and cytokine and granzyme profiles in peripheral blood from a group of stable lung transplant patients and control subjects using multiparameter flow cytometry.

RESULTS

There was a significant increase in NKT-like cells in transplant patients compared with control subjects (6.8 ± 4.9 vs 0.8 ± 0.2% lymphocytes respectively). There was an increase in the numbers of NKT-like cells producing IFN-γ, TNF-α, IL-2 IL-17, granzyme and perforin in transplant patients compared with controls. Immunosuppressant drugs were less effective at inhibiting IFN-γ and TNF-α production by T and NKT-like cells than NK cells in vitro.

CONCLUSIONS

Current therapeutics is inadequate at suppressing NKT-like cell numbers and their production of pro-inflammatory mediators known to be associated with graft rejection. Alternative therapies that specifically target NKT-like cells may improve patient morbidity.

Authors+Show Affiliations

Department of Thoracic Medicine, Royal Adelaide Hospital, South Australia, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21995313

Citation

Hodge, Greg, et al. "Increased Natural Killer T-like Cells Are a Major Source of Pro-inflammatory Cytokines and Granzymes in Lung Transplant Recipients." Respirology (Carlton, Vic.), vol. 17, no. 1, 2012, pp. 155-63.
Hodge G, Hodge S, Li-Liew C, et al. Increased natural killer T-like cells are a major source of pro-inflammatory cytokines and granzymes in lung transplant recipients. Respirology. 2012;17(1):155-63.
Hodge, G., Hodge, S., Li-Liew, C., Reynolds, P. N., & Holmes, M. (2012). Increased natural killer T-like cells are a major source of pro-inflammatory cytokines and granzymes in lung transplant recipients. Respirology (Carlton, Vic.), 17(1), 155-63. https://doi.org/10.1111/j.1440-1843.2011.02075.x
Hodge G, et al. Increased Natural Killer T-like Cells Are a Major Source of Pro-inflammatory Cytokines and Granzymes in Lung Transplant Recipients. Respirology. 2012;17(1):155-63. PubMed PMID: 21995313.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased natural killer T-like cells are a major source of pro-inflammatory cytokines and granzymes in lung transplant recipients. AU - Hodge,Greg, AU - Hodge,Sandra, AU - Li-Liew,Chien, AU - Reynolds,Paul N, AU - Holmes,Mark, PY - 2011/10/15/entrez PY - 2011/10/15/pubmed PY - 2012/3/9/medline SP - 155 EP - 63 JF - Respirology (Carlton, Vic.) JO - Respirology VL - 17 IS - 1 N2 - BACKGROUND AND OBJECTIVE: Natural killer T (NKT)-like cells are a small but significant population of T lymphocytes; however, their role in lung transplant and the effect of current immunosuppressive agents on their function is largely unknown. We have previously shown lung transplant rejection was associated with an increase in peripheral blood T cell γ-interferon (IFN-γ), tumour necrosis factor-α (TNF-α) and granzyme B. NKT-like cells are a source of these pro-inflammatory mediators and as such may be involved in lung transplant pathology. METHODS: We analysed NKT-like cell numbers and cytokine and granzyme profiles in peripheral blood from a group of stable lung transplant patients and control subjects using multiparameter flow cytometry. RESULTS: There was a significant increase in NKT-like cells in transplant patients compared with control subjects (6.8 ± 4.9 vs 0.8 ± 0.2% lymphocytes respectively). There was an increase in the numbers of NKT-like cells producing IFN-γ, TNF-α, IL-2 IL-17, granzyme and perforin in transplant patients compared with controls. Immunosuppressant drugs were less effective at inhibiting IFN-γ and TNF-α production by T and NKT-like cells than NK cells in vitro. CONCLUSIONS: Current therapeutics is inadequate at suppressing NKT-like cell numbers and their production of pro-inflammatory mediators known to be associated with graft rejection. Alternative therapies that specifically target NKT-like cells may improve patient morbidity. SN - 1440-1843 UR - https://www.unboundmedicine.com/medline/citation/21995313/Increased_natural_killer_T_like_cells_are_a_major_source_of_pro_inflammatory_cytokines_and_granzymes_in_lung_transplant_recipients_ L2 - https://doi.org/10.1111/j.1440-1843.2011.02075.x DB - PRIME DP - Unbound Medicine ER -