Up‐regulation of alternate co‐stimulatory molecules on proinflammatory CD28null T cells in bronchiolitis obliterans syndrome. (6th June 2013)

• Record Type: Journal Article
• Authors: Hodge, G.; Hodge, S.; Ahern, J.; Holmes‐Liew, C.‐L.; Reynolds, P. N.; Holmes, M.
• Is Part Of: Clinical and experimental immunology. Volume 173:Number 1(2013:Jul.)
• Page Start: 150
• Page End: 160
• Publication Date: 2013-06-06
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12081
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Bronchiolitis 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 (<italic>n</italic> = 38), patients with BOS (<italic>n</italic> = 20) and healthy controls (<italic>n</italic> = 10). There was a significant increase in the percentage of CD4/28<sup>null</sup> and CD8/28<sup>null</sup> 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<sup>+</sup> T cells and CD137 and CD152 on CD8<sup>+</sup> T cells. There was a significant correlation between increased CD28<sup>null</sup>/CD137 T cells producing IFN‐γ, TNF‐α with BOS grade (<italic>r</italic> = 0·861, <italic>P</italic> < 0·001 for CD28<sup>null</sup>/CD137 IFN‐γ/CD8) and time post‐transplant (<italic>r</italic> = 0·698, <italic>P</italic> < 0·001 for CD28<sup>null</sup>/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<sup>+</sup> and CD8<sup>+</sup> T cells. Therapeutic targeting of alternate co‐stimulatory molecules on peripheral blood CD28<sup>null</sup> T cells and monitoring response using these assays may help in the management of patients with BOS.</p> </abstract>