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BLTR1 Is Decreased in Steroid Resistant Pro-Inflammatory CD28nullCD8+ T Lymphocytes in Patients with COPD-The
Greg Hodge1,2, Hubertus Jersmann1,2, Mark Holmes1,2
1Chronic Inflammatory Lung Disease Laboratory, Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide 5001, Australia.
Introduction:
Pro-inflammatory CD8+ T cells are increased in the lungs and also in the peripheral circulation of both smokers and chronic obstructive pulmonary disease (COPD) patients. The reason for this is unclear but has been described as a spillover from cells in the lungs that may cause the systemic inflammation noted in COPD. We have recently shown an increase in steroid-resistant CD28nullCD8+ senescent lymphocytes in the lungs and peripheral blood in COPD. Leukotreine B4 (LB4) receptor 1 (BLTR1) is involved in recruitment of CD8+ T cells to sites of inflammation, and we hypothesized that it may be involved in the migration of these senescent lymphocytes from the lungs in COPD.
Methods:
Via flow cytometry and Western blot BLTR1, IFNγ, and TNFα expression were measured in peripheral blood, BAL, and large proximal and small distal airway CD28±, CD8± T, and NKT-like cells from COPD patients and healthy control subjects (±prednisolone) following in vitro stimulation. Chemotaxis of leucocyte subsets was determined (±LB4 ± prednisolone).
Results:
There was an increase in BLTR1-CD28nullCD8+ lymphocytes in the lungs and blood in patients with COPD compared with controls. BLTR1-CD28nullCD8+ T and NKT-like cells produce more IFN/TNF than BLTR+ cells and fail to migrate to LTB4. Treatment with 1 µM prednisolone in vitro resulted in upregulation of BLTR1 expression in pro-inflammatory CD28nullCD8+ cells and migration to LB4.
Conclusions:
Loss of BLTR1 is associated with an increased inflammatory potential of CD28nullCD8+ T cells and may allow these pro-inflammatory steroid-resistant cells to migrate to peripheral blood. Treatment strategies that upregulate BLTR1 may reduce systemic inflammation and associated co-morbidity in patients with COPD.
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