期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 121, 期 4, 页码 864-871出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2008.01.035
关键词
central memory T cell; CD122; CD25; corticosteroid-insensitive asthma; effector memory T cell
资金
- NHLBI NIH HHS [P01 HL036577-21A15977, HL-61005, P01 HL036577, HL-36577] Funding Source: Medline
- PHS HHS [A1-52381] Funding Source: Medline
Background: Leukotriene B-4 (LTB4) is a potent inflammatory lipid mediator that binds to LTB4 receptor 1 (BLT1). Ligation of BLT1 by LTB4 plays an important role in the recruitment of effector memory CD8(+) T cells into the airways of sensitized and challenged mice. Objectives: The effects of the corticosteroid dexamethasone (DEX) on BLT1-expressing effector memory CD8(+) T cells and effector memory CD8(+) T cell-mediated airway hyperresponsiveness (AHR) and allergic inflammation were determined. Methods: Effector memory CD8(+) T cells were generated from ovalbumin(257-264)-primed mononuclear cells from OT-1 mice in the presence of IL-2. In some cultures DEX was added. The effects of DEX on BLT1 expression, LTB4-induced Ca2+ influx, phosphorylation of extracellular signal-regulated kinase 1/2, chemotaxis, and effector memory CD8(+) T cell-mediated AHR were examined. Results: DEX-treated effector memory CD8(+) T cells showed significant increases in surface expression of BLT1, LTB4-induced intracellular Ca2+ influx, phosphorylation of extracellular signal-regulated kinase 1/2, and chemotaxis. Upregulation of BLT1 by DEX was accompanied by increased IL-2 receptor expression. Adoptive transfer of DEX-treated effector memory CD8(+) T cells into ovalbumin-sensitized and ovalbumin-challenged CD8(-/-) mice resulted in significant increases in AHR, allergic inflammation, goblet cell metaplasia, and numbers of both CD8(+) and CD4(+) T cells in the bronchoalveolar lavage fluid and lungs. Conclusions: Corticosteroids upregulate BLT1 on effector memory CD8(+) T cells and related signaling pathways and potentiate allergic airway inflammation and AHR induced by these cells.
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