The Editors' choiceCorticosteroids enhance CD8+ T cell–mediated airway hyperresponsiveness and allergic inflammation by upregulating leukotriene B4 receptor 1
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Animals
Homozygous CD8α−/− mice, OT-1 mice expressing a transgenic T-cell receptor specific for ovalbumin (OVA)257-264 (SIINFEKL) peptide, and C57BL/6 wild-type (WT) mice were purchased from the Jackson Laboratory (Bar Harbor, Me). BLT1−/− mice were backcrossed into the C57BL/6 background for more than 9 generations.6 BLT1-deficient OT-1 mice were generated by mating BLT1−/− mice with OT-1 mice. All mouse protocols used in this study were approved by the Institutional Animal Care and Use Committee of
CD8+ TEFFs are resistant to DEX
We33 first confirmed that activated CD8+ T cells were resistant to DEX, whereas activated CD4+ T cells were sensitive to DEX. CD8+ T cells treated with anti-CD3/anti-CD28 in the presence of IL-2 were resistant to 100 nM of DEX, whereas similarly treated CD4+ T cells showed a rapid decrease in cell numbers (see Fig E1, A, in the Online Repository at www.jacionline.org). Next we examined the effect of DEX on IL-2– or IL-15–dependent cell growth of activated CD8+ T cells. DEX treatment did not
Discussion
In the present study we investigated the susceptibility of CD4+ or CD8+ T cells to DEX and the effects of DEX treatment on the phenotypic and functional properties of CD8+ TEFFs during their differentiation in vitro and their effects on AHR and allergic airway inflammation in vivo. The results showed that activated CD8+ T cells were more resistant to DEX than CD4+ T cells in the presence of IL-2 and that DEX treatment upregulated BLT1 expression on TEFFs in a dose-dependent manner, likely
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Supported by National Institutes of Health grants HL-36577 and HL-61005, by US Environmental Protection Agency grant R825702 (to E.W.G.), and by National Institutes of Health grant A1-52381 (to B.H.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Heart, Lung, and Blood Institute or the National Institutes of Health.
Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.