title: Increased natural killer T-like cells are a major source of pro-inflammatory cytokines and granzymes in lung transplant recipients.
abstract: 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: Department of Thoracic Medicine, Royal Adelaide Hospital, South Australia, Australia.
authors: Greg
authors: G
authors: Hodge
authors: Sandra
authors: S
authors: Hodge
authors: Chien
authors: C
authors: Li-Liew
authors: Paul N
authors: PN
authors: Reynolds
authors: Mark
authors: M
authors: Holmes
mesh_terms: D016207:Cytokines / Q000097:blood* / Q000187:drug effects; D005260:Female; D005541:Forced Expiratory Volume; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology*; D053804:Granzymes / Q000097:blood* / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000097:blood; D020381:Interleukin-17 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D016040:Lung Transplantation / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D053804:Granzymes