Human type-2 CD8⁺ T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia-a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8⁺CRTH2⁺ (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D₂ (PGD₂) and cysteinyl leukotriene E₄ (LTE₄) are also increased in the airways of the same group of patients. In vitro PGD₂ and LTE₄ function synergistically to trigger Tc2 cell recruitment and activation in a TCR-independent manner. These lipids regulate diverse genes in Tc2 cells inducing type-2 cytokines and many other pro-inflammatory cytokines and chemokines, which could contribute to eosinophilia. These findings are consistent with an important innate-like role for human Tc2 cells in severe eosinophilic asthma and suggest a potential target for therapeutic intervention in this and other diseases.

中文翻译：

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脂质介质在严重嗜酸性粒细胞性哮喘中协同激活促炎 2 型 CD8+ T 淋巴细胞。

人类 2 型 CD8 ⁺ T 细胞是一种在过敏性疾病中具有潜在重要作用的细胞群。我们在严重哮喘伴持续性气道嗜酸性粒细胞增多症的背景下对此进行了调查——这是一种与高恶化风险和对 2 型细胞因子靶向治疗的反应相关的表型。在两个独立的队列中，我们表明，与 Th2 细胞相比，分泌 2 型细胞因子的 CD8 ⁺ CRTH2 ⁺ (Tc2) 细胞在严重嗜酸性粒细胞性哮喘的血液和气道中富集。在同一组患者的气道中，前列腺素 D ₂ (PGD ₂ ) 和半胱氨酰白三烯 E ₄ (LTE ₄ ) 的浓度也有所增加。体外 PGD ₂和 LTE ₄协同作用，以独立于 TCR 的方式触发 Tc2 细胞募集和激活。这些脂质调节 Tc2 细胞中的不同基因，诱导 2 型细胞因子和许多其他促炎细胞因子和趋化因子，这可能导致嗜酸性粒细胞增多。这些发现与人类 Tc2 细胞在严重嗜酸性粒细胞性哮喘中的重要先天样作用一致，并提出了对这种疾病和其他疾病进行治疗干预的潜在目标。