Loss of glucocorticoid receptor from pro-inflammatory T cells after lung transplant

• Published in: The Journal of heart and lung transplantation Vol. 33; no. 9; pp. 957 - 962
• Main Authors: Hodge, Greg, PhD, Hodge, Sandra, PhD, Holmes-Liew, Chien Li, MBBS, MCSc, FRACP, Reynolds, Paul N., PhD, MD, MBBS, Holmes, Mark, MClinSc, MBBS
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2014
• Subjects: Adult; Case-Control Studies; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Dose-Response Relationship, Drug; Down-Regulation; GCR; Glucocorticoids - therapeutic use; Humans; IFN-γ; Inflammation - metabolism; Interferon-gamma - metabolism; Lung Diseases - surgery; lung transplant; Lung Transplantation; Middle Aged; Natural Killer T-Cells - metabolism; Natural Killer T-Cells - pathology; Postoperative Period; Prednisolone - therapeutic use; Receptors, Glucocorticoid - metabolism; Surgery; T cells; Time Factors; TNF-α; Tumor Necrosis Factor-alpha - metabolism; IFN-γ; TNF-α; T cells; lung transplant; GCR
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2014.05.004

Background Pro-inflammatory cytokines in T and natural killer T (NKT)-like cells increase with time post-transplant in otherwise stable patients, suggesting that some patients become relatively resistant to immunosuppressants such as glucocorticoids (GC). We hypothesized that GC receptor (GCR) would be down-regulated in peripheral blood pro-inflammatory T and NKT-like cells after lung transplantation and loss of GCR would correlate with time post-transplant. Methods Blood was collected from 17 stable lung transplant patients and 17 healthy, aged-matched controls. Intracellular GCR expression and pro-inflammatory cytokines were determined using flow cytometry. Results There was a loss of GCR in CD8+ and CD8− T and NKT-like cells in transplant patients compared with control subjects (transplants 37 ± 9%, controls 47 ± 12%; GCR+ CD8+ and CD8− T cells: transplants 39 ± 13%, controls 58 ± 13%). Loss of GCR was associated with a greater percentage of T cells producing interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) but not NKT-like cells. There was a correlation between the percentage of GCR-negative T cells with months post-transplant ( R = 0.519, p = 0.033) and dose of prednisolone ( R = 0.775, p = 0.038). Conclusions Time post-transplant and prednisolone dose correlate with loss of GCR in pro-inflammatory T cells in stable transplant patients, suggesting the need for reassessment of the long-term use of steroids after lung transplant in view of their attendant significant side effects.