Hodge, G.Hodge, S.Ahern, J.Liew, C.Reynolds, P.Holmes, M.2013-08-282013-08-282013Clinical and Experimental Immunology, 2013; 173(1):150-1600009-91041365-2249http://hdl.handle.net/2440/79564Bronchiolitis obliterans syndrome (BOS) is associated with lack of immunosuppression of T cell proinflammatory cytokines and increased T cell granzyme B. Repeated antigen-driven proliferation down-regulates T cell CD28. We hypothesized that down-regulation of CD28 and up-regulation of alternate co-stimulatory molecules (CD134, CD137, CD152 and CD154) on T cells may be associated with BOS. Co-stimulatory molecules, granzyme B, perforin and intracellular cytokines were measured by flow cytometry on T cells from stable lung transplant patients (n = 38), patients with BOS (n = 20) and healthy controls (n = 10). There was a significant increase in the percentage of CD4/28null and CD8/28null T cells producing granzyme B, interferon (IFN)-γ and tumour necrosis factor (TNF)-α in BOS compared with stable patients. Down-regulation of CD28 was associated with steroid resistance and up-regulation of CD134, CD137, CD152 and CD154 on CD4+ T cells and CD137 and CD152 on CD8+ T cells. There was a significant correlation between increased CD28null/CD137 T cells producing IFN-γ, TNF-α with BOS grade (r = 0•861, P < 0•001 for CD28null/CD137 IFN-γ/CD8) and time post-transplant (r = 0•698, P < 0•001 for CD28null/CD137 IFN-γ/CD8). BOS is associated with down-regulation of CD28 and up-regulation of alternate co-stimulatory molecules on steroid-resistant peripheral blood proinflammatory CD4+ and CD8+ T cells. Therapeutic targeting of alternate co-stimulatory molecules on peripheral blood CD28null T cells and monitoring response using these assays may help in the management of patients with BOS.en© 2013 British Society for ImmunologyBOSCD28nulllung transplantproinflammatory T cellsJournal article002013023910.1111/cei.120810003200324000172-s2.0-8487878874219017Hodge, S. [0000-0002-3602-9927] [0000-0002-9401-298X]Reynolds, P. [0000-0002-2273-1774]