CD8 cell subset count linked to airway obstruction in asthma
medwireNews: The frequency of a subset of CD8 T lymphocytes expressing the high-affinity receptor for LTB4 (BLT1) and producing interleukin (IL)-13 is significantly greater in the airways of patients with asthma than healthy people, a study finds.
The accumulation of these cells was associated with a higher degree of airway obstruction, suggesting they may play a significant role in the pathogenesis of asthma, the authors say.
"These findings extend observations from recent experimental studies that established an important pathogenic role for effector memory CD8 T cells in the development of AHR [airway hyperresponsiveness] and allergic airway inflammation and preliminary findings of a similar subset of CD8 cells in asthmatic airway," explain Azzeddine Dakhama (National Jewish Health, Denver, Colorado, USA) and colleagues in Allergy.
The team took bronchoalveolar lavage (BAL) cells from 39 patients with asthma and 28 healthy controls, stimulated them with phorbol ester and ionomycin in the presence of brefeldin A, and stained them for CD8, BLT1, and intracellular IL-13.
The proportion of lymphocytes that stained positive for CD8 was significantly higher in the BAL fluid of patients with asthma than controls (31.8 vs 17.5%) while the difference in absolute numbers did not reach statistical significance.
A majority of BAL CD8 lymphocytes expressed the BLT1 receptor in both groups. However, the frequency of IL-13 producing BLT1-positive CD8 lymphocytes was a significant threefold higher in the BAL of patients with asthma than in the BAL of controls (16.2 vs 5.3%).
This was accompanied by significantly greater absolute numbers of these cells in the BAL fluid of patients with asthma compared with controls (1170 vs 270/mL) - a frequency that directly correlated with serum immunoglobulin levels and reticular basement membrane thickness.
The frequency of IL-13-producing BLT1-positive CD8 lymphocytes had a significant inverse relationship with the predicted percentage values of forced expiratory volume in 1 second (FEV1) as well as forced expiratory flow between 25% and 75% of forced vital capacity (mid-expiratory flow).
Notably, only the IL-13-producing BLT1-positive subset of CD8 lymphocytes was inversely correlated with FEV1 and mid-expiratory flow.
"IL-13 is a critical mediator of AHR and mucus hyperproduction, and CD8 T lymphocytes are potentially less sensitive than CD4 lymphocytes to conventional anti-inflammatory corticosteroid therapy," conclude the authors.
"Further studies targeting this subset of effector CD8 lymphocytes or the pathway responsible for their accumulation and effector function in the lung are necessary to establish a causative role in asthma."
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By Peter Sergo, medwireNews Reporter