Time post-lung transplant correlates with increasing peripheral blood T cell granzyme B and proinflammatory cytokines

Immunosuppression therapy following lung transplant fails to prevent chronic rejection/bronchiolitis obliterans syndrome, which we have shown is associated with lack of suppression of peripheral blood T cell granzyme B, interferon (IFN)- and tumour necrosis factor (TNF)-. We hypothesized that these proinflammatory mediators may increase with time post-transplant in otherwise stable patients before clinical signs of declining lung function, and patients experiencing declining lung function would show a further increase in these mediators. Intracellular cytokine profiles and granzyme B were investigated in T cells in whole blood and airways from lung transplant patients using flow cytometry. There was a significant negative correlation between forced expiratory volume in 1 s (FEV1), drug dose and time post-transplant. A significant correlation between increased granzyme B, IFN-, interleukin (IL)-2 and TNF- and time post-transplant was noted in peripheral blood T cells but not lung T cells from stable patients. Patients with similar drug dose but experiencing declining FEV1 showed a further increase in peripheral blood T cell IFN-, IL-2 and TNF-. Time post-lung transplant correlates with increasing peripheral blood T cell granzyme B and proinflammatory cytokines. Declining FEV1 is associated with a further increase in these proinflammatory mediators. Drugs that reduce these inflammatory mediators effectively may reduce the incidence of chronic graft rejectionG. Hodge, S. Hodge, C. Li-Liew, D. Chambers, P. Hopkins, P. N. Reynolds and M. Holme