Increased natural killer T-like cells are a major source of pro-inflammatory cytokines and granzymes in lung transplant recipients

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 gamma-interferon (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) 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 NKTlike cells producing IFN-gamma, TNF-alpha, IL-2 IL-17, granzyme and perforin in transplant patients compared with controls. Immunosuppressant drugs were less effective at inhibiting IFN-gamma and TNF-alpha 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.